Systems and methods for structuring the financing of high cost therapies

ABSTRACT

Presented herein are systems and methods for structuring the financing of high cost therapies such as GCTs to address the issues of high-upfront cost (affordability), uncertain durability of the treatment, and portability/transferability of the liability. In certain embodiments, the systems and methods described herein involve a combination of (a) a uniquely-designed, multi-year structured loan that facilitates portability, (b) a performance-based guarantee of efficacy in the form of a value based agreement that may be tied to the tenure of the loan, and (c) securitization of the loan.

CROSS-REFERENCE

This application claims benefit of and priority to U.S. ProvisionalApplication No. 63/173,916 filed Apr. 12, 2021 and U.S. ProvisionalApplication No. 63/187,830 filed May 12, 2021, each of which is entirelyincorporated herein by reference for all purposes. This application is adivisional application of U.S. patent application Ser. No. 17/327,604filed May 21, 2021.

FIELD

This invention relates generally to systems and methods for structuringthe financing of high cost therapies (HCTs) in a manner that providesfor transferability. More particularly, in certain embodiments, theinvention relates to systems and methods for structuring one or moreinstruments of an HCT financing, where the HCT financing includes amulti-year structured loan, a value based agreement (e.g., a performanceagreement, a warranty, or other insurance product), and asecuritization.

BACKGROUND

There are an array of challenges associated with expanding the usage ofpotentially curative high-cost pharmaceuticals, specifically gene andcellular therapies (GCTs) with broad applicability to the entirespectrum of high cost therapies (HCTs). Factors threatening to limit thedeployment of these cures include (a) their high cost, (b) uncertaintyregarding the efficacy/durability of the therapy, and (c) the potentialthat beneficiaries will switch employers/insurers.

Examples of these high cost therapies include Zolgensma ($2.1 millionone-time cost) manufactured by AveXis, Inc., Zokinvy ($1.0 million/yr)manufactured by Eiger BioPharmaceuticals, Danyelza ($980,000/yr)manufactured by Y-mAbs Therapeutics, Inc., Myalept ($890,000/yr)manufactured by Aegerion Pharmaceuticals, Luxturna ($850,000 one-timecost) manufactured by Spark Therapeutics, Folotyn ($790,000/yr)manufactured by Acrotech Biopharma, Brineura ($730,000/yr) manufacturedby BioMarin Pharmaceuticals, Jivi ($720,000/yr) manufactured by BayerPharmaceuticals, Inc., Blincyto ($710,000/yr) manufactured by Amgen,Inc., Ravicti ($700,000/yr) manufactured by Horizon Therapeutics,Soliris ($680,000/yr) manufactured by Alexion Pharmaceuticals, Inc., andAbecma ($420,000 one-time cost) manufactured by Bluebird Bio. Zolgensmais a one-time curative therapy to treat children with spinal muscularatrophy. Zokinvy is a treatment for Hutchinson-Gilford progeriasyndrome, which costs about $717 per capsule, with patients typicallytaking four capsules daily. Danyelza is a treatment for patients withneuroblastoma in the bone or bone marrow, which costs about $20,000 pervial, with typical use of 48 vials per year. Myalept is a treatment forgeneralized lipodystrophy, with typical use being 14 vials per month.Luxturna is a gene therapy that treats a form of retinal dystrophy andis a one-time therapy (one vial administered into each eye). Folotyn isused to treat peripheral T-cell lymphoma, and typical use is 45 vials ofthe drug per year. Brineura is used to treat a form of Batten disease inpediatric patients, with recommended dosage of 300 mg every two weeks.Jivi is an anti-hemophilic factor therapy for patients with hemophiliaA. Blincyto is used to treat a rare form of acute lymphoblasticleukemia, with typical use being about 168 vials per year. Ravicti isused to treat urea cycle disorders, which are genetic conditions thatresult in high levels of ammonia in the blood; patients are typicallygiven 132 bottles per year at a cost of about $5270 per bottle. Solirisis used to treat certain blood disorders that result in the destructionof red blood cells with recommended dose of about 1200 mg every twoweeks. Abecma is a genetically modified autologous T cell immunotherapyfor treatment of adult patients with relapsed or refractory multiplemyeloma, administered as a one-time infusion. Some of these drugs can beself-administered and others must be administered by a healthcareprovider.

Of particular interest, and challenge with respect to financing, areone-time dose high cost GCT drugs. As the number of such GCTs approvedby the US Food and Drug Administration (FDA) to treat orphan andprevalent indications increases over the next decade, the economicburden placed on health benefit payers will grow substantially, as thecosts of these therapies can exceed $2 million for the one-time dose.The initial burden is likely to be greatest amongst middle marketself-insurers with covered beneficiaries who would benefit from theadministration of a GCT. Unlike many large, well-capitalized companieswith hundreds—if not thousands—of beneficiaries, these smaller entitiesare often insufficiently capitalized to handle a substantial near-termdisbursement. Even with the assistance of stop-loss protection orreinsurance, the triggering of those policies typically results in amaterial premium increase to the self-insurer in addition to thelasering of the GCT beneficiary from the policy, rendering theself-insurer exposed to any and all future healthcare costs incurred bythat individual.

In addition to the elevated cost, there is also no guarantee that a GCTwill be effective in every individual to whom it is administered.Current failure rates for the few commercialized and late developmentstage GCTs can be high. Further, visibility regarding durability (i.e.how long the treatment benefit will last) may be poor even for thosetherapies which are deemed to be clinically efficacious in the shortterm. Payers will incur liabilities for therapies that may ultimatelynot alleviate the burden of disease. In the event a GCT fails, manybeneficiaries will resort back to high cost standards of care, the costof which will still be borne by the payer who now has taken on theadditional liability of a failed GCT.

Beyond cost and uncertain durability, all payers, even larger,well-capitalized self-insurers, will be exposed to risk if a GCT-treatedbeneficiary departs from their health plan. In such circumstances,payers may continue to pay for a GCT only to have that coveredbeneficiary leave the plan because of a change in employment. In suchcircumstances, the payer has incurred an inordinate portion of theliability for the beneficiary's treatment. This transferability riskhighlights the economic timing mismatch between a large expense borne bythe payer and future revenue streams (i.e., premium payments) and healthbenefits.

In short, the cost of GCTs creates a potentially untenable situation formany payers and may hinder their ability to provide benefits to allcovered beneficiaries on a go-forward basis. This will become of greaterconcern as GCTs proliferate over the next years.

SUMMARY

Presented herein are systems and methods for structuring the financingof high cost therapies such as GCTs to address the issues ofhigh-upfront cost (affordability), uncertain durability of thetreatment, and portability/transferability of the liability. In certainembodiments, the systems and methods described herein involve acombination of (a) a uniquely-designed, multi-year structured loan thatfacilitates portability, (b) a performance-based guarantee of efficacyin the form of a warranty that may be tied to the tenure of the loan,and (c) securitization of the loan.

Loan

In certain embodiments, the loan provides a mechanism by which payerscan spread the cost of GCTs over time through manageable periodicprincipal and interest payments. Extending the payment period in thismanner more appropriately matches the expense with both the presumedbenefits of the therapy and the premium streams received by payers.

Although various embodiments of the loan described herein provide adegree of standardization, the terms are flexible enough to addresspeculiarities of the covered therapeutic and can be modified based onneeds of both the borrower and manufacturer. Terms may be calculatedutilizing various stochastic, algorithmic, and/or machine learning(and/or other forms of artificial intelligence (AI)) methodologies whichutilize inputs including, but not limited to, one or more of thefollowing: the total cost of the therapy (inclusive of service andadministration costs), the credit rating of the borrower, the currentdebt service of the borrower, the ability of the borrowing firm tocollateralize the loan, the financial solvency and cash flow generatingcapability of the borrowing firm, the desire of the manufacturer toprovide subvention, the amount, if any, of the manufacturer holdback,the projected efficacy of the GCT, the nature, cost and terms of anassociated warranty, the duration of the warranty, the existence, ifany, and cost of a current, non-GCT or GCT standard of care therapy, thelevel of interest rate benchmarks such as LIBOR (London InterbankOffered Rate) for variable rate loans, prevailing market interest ratesfor loans of similar tenor and risk profile, market-wide default rates,the existence, if any, of prepayment penalties, the size of any upfrontdraws and other metrics deemed necessary by the lender.

In certain embodiments, the principal amount of the loan will include anupfront draw that is equivalent to a percentage of the cost of the GCTplus the associated value based agreement (VBA) premium (e.g.,performance agreement, warranty, or other insurance product premium),initial outcomes benefit administrator (OBA) fees, certain approvedcosts and expenses of pre-therapy therapeutic treatments and services,procedure-related costs, and an arrangement fee. The size of thisupfront draw may be calculated so as to not trigger any best-price andanti-kickback features of federal, state, local, and/or other applicablelaw. In certain embodiments, the lender can work with HCT (e.g., GCT)manufacturers to apply for a unique National Drug Code (NDC) that notonly uniquely identifies the GCT, but also the mechanism of paymentthrough the HCT financing structure. The mechanism of financing may bedescribed or otherwise referenced in the packaging of the drug, forexample. While the NDC coding scheme does not directly code for paymentmechanism, a unique NDC can be created for various packaging constructsof the GCT. For example, if such construct is solely sold throughdistribution channels in which the HCT financing structure is utilizedas the payment mechanism, the NDC, ipso facto, is tied to the HCTfinancing structure.

In certain embodiments, a determination period is established inconjunction with the payer and GCT manufacturer (e.g., two weeks orother time period following the administration of the GCT) to assesswhether the therapy has successfully been transfected into thepatient/beneficiary or whether it has generated an adverse responsewhich would render the therapy ineffective or undesired. If theadministration is determined by the OBA to be indicatively successful, asecond draw totaling the remainder of the loan value minus apredetermined manufacturer holdback will be paid. At this point, theloan will be considered seasoned and the borrower will commence makingperiodic installments of principal and interest repayment. If, however,the administration of the therapy is assessed to be unsuccessful duringthe determination period, the warranty will be triggered and the payoutof the warranty will be used to compensate the lender for any upfrontdraw that has been paid and any prepayment penalty associated with earlytermination of the loan.

In certain embodiments, a contractually defined “episode of care” is setto match the instrument's tenor. In certain embodiments, the episode ofcare will begin when the patient/beneficiary is prescribed the therapy,or at the execution of the term sheet or loan documents, or at anotherpoint in time decided upon by the lender and key stakeholders (e.g., thepayer, manufacturer, etc.). The episode of care will continue forward asthe patient/beneficiary continues to be monitored by an external OBA toassess whether the GCT is providing the efficacy contractually agreed toby the manufacturer, as expressed by the terms of the warranty, andduring which the loan recipient is continuing to make periodic paymentsof principal and interest. As such, the episode of care also includespost-therapeutic treatments and services, as recommended by themanufacturer and agreed to by the payer for monitoring and supportingthe patient/beneficiary. The total cost of the loan could cover not onlythe cost of the therapeutic itself, but also the pre- andpost-therapeutic health care costs associated with the indication andGCT therapy, such as healthcare professional visits, medical tests andscans, and other healthcare costs related to the patient/beneficiarydiagnosis and/or therapeutic. During the episode of care, the diagnosisof the patient/beneficiary is considered to be unchanged. Thisdetermination of the episode of care as part of the loan term structureis crucial to the notion of portability of the HCT financing structure.Defining the episode of care establishes a pre-existing condition, whichis a key component of the Affordable Healthcare Act.

Warranty or other Value Based Agreement (VBA)

To mitigate the risk of GCT therapy faced by payers and to offset theloan liability in the event of therapeutic inefficacy, in certainembodiments, the HCT financing also includes a performance guarantee inthe form of a lender's warranty, a manufacturer supplied warranty, orother value based agreement (VBA), or third-party supplied warranty orVBA (“warranty”). In certain embodiments, the warranty is structured toguarantee the efficacy of GCT therapy using predefined, measurable,reproducible and verifiable criteria (serum biomarkers, functionaltests, etc.) agreed to by both the manufacturer and payer/self-insurerin advance of the administration of the GCT. These measures, which willbe assessed periodically by a third-party outcomes-based administrator(OBA), constitute the criteria by which the GCT will be consideredeffective. If a therapy is assessed as ineffective during the period inwhich the warranty is active, the warranty will be triggered and thepayer will receive a disbursement as stipulated under the terms of thewarranty. In most cases, the disbursement can be used to directlycompensate the payer for any remaining loan liability, which may includecompensation for the upfront draw and the prepayment penalty; however,the warranty disbursement may also be used to cover an equivalent value(of the remaining loan liability) in costs incurred by the payer inreverting the covered patient/beneficiary to standard of care therapy(payment in kind).

The lender may work in conjunction with third party insurers to providethe warranty or it may work directly with manufacturers to establish thenecessary corporate and regulatory structures that are required toimplement a successful warranty program that does not infringe upon CMSBest Price (Centers for Medicare and Medicaid Services Best Price). Insuch instances where the GCT manufacturer chooses to directly issue thewarranty, the lender, or an associated designee of the lender, willassist the manufacturer in developing warranty terms that are based bothon the therapeutic performance of the GCT in clinical and post-marketingtrials and which are deemed likely to maximize demand interest in themarket. Like the loan, the term structure of the warranty can becalculated utilizing various stochastic, algorithmic and artificialintelligence (AI) methodologies which utilize inputs including, but notlimited to, one or more of the following: the availability of relevantefficacy data provided by the manufacturer, the risk tolerance of themanufacturer, the cost of the GCT, the availability, if any, and cost ofa standard of care alternative therapy, the prevalence of the disease,payer survey data, and any other inputs deemed necessary by both thelender and the manufacturer.

In certain embodiments in which the warranty is manufacturer-issued, thelender, or its designee, can work with the manufacturer to create andstructure an incorporated cell captive—if one does not already exist—alegal subsidiary entity to which the warranty can be transferred inexchange for a premium and the receipt of a contractual liabilityinsurance policy. The cell captive may be required to have risk-basedcapital ratios commensurate to the level of risk assumed in combinationof cash and lines of credit. The cell captive can subsequently enterinto an agreement with a managing general underwriter selected by themanufacturer in consultation with the lender to run the insuranceoperations of the captive. The captive may, at its discretion, purchasereinsurance to spread the risk of non-efficacy to the broader market.The lender may at some future time work with a third-party insuranceunderwriter to whom the manufacturer can directly transfer the warrantyliability for a premium. The underwriter may require the manufacturer tocontribute to a risk pool that will be utilized to pay claims onwarranties that have been triggered by the inefficacy of their product.

In certain embodiments, a third-party outcomes-based administrator(OBA), selected with the consent of the payer and GCT manufacturer,regularly monitors (e.g., at predetermined times, specific to the GCT)the patient/beneficiary according to the terms stipulated by thewarranty to access GCT efficacy. The OBA adjudicates whether the payoutterms of the warranty have been triggered and, if so, direct the liableparty to make disbursements as stipulated. Warranties are structured soas to permit transfer to another party in the event that thepatient/beneficiary is transferred to another payer.

Securitization

In certain embodiments, once a sufficient HCT financing loan portfoliohas been created (with “sufficiency” defined, for example, in terms ofthe risk profile and diversity of the borrowers, the diversity of GCTscovered, the diversity of GCT manufacturers, in addition to othermetrics), the lender will bundle these loans for the purposes ofsecuritization and distribution to the broader financial markets. Forexample, the securitization basket may comprise 200-300 HCT financingloans with a notional value of 300MM-500MM USD. Credit rating, averagecoupon, position sizing, and the like, can be determined at the time ofcreation. Tranching of the loan cash flows can be determined during thecreation of the securitization and subject to various market conditionsthat would affect the attractiveness of the securities to the market.Loans associated with multiple GCTs, various payer types, differing loantenors, and the like, may be ideal to achieve the maximumdiversification benefit from the total portfolio and to reduce the riskprofile of both the overall loan basket as well as the individualtranches.

In certain embodiments, the process of securitization provides amechanism to offboard risk of the HCT financing to the market andfacilitates potentially lower interest rates for individual loans topayers/borrowers.

It is believed the proposed HCT financing payment solution for GCTsprovided herein is the first to combine a multi-year structure loan, awarranty, and a securitization. It is also believed that the proposedsolution described herein is the first to contractually link the termstructure of the financial instrument with the episode of care, therebyestablishing and/or defining a pre-existing condition, renderingtransferability possible. While embodiments are described hereinprimarily with respect to GCTs (e.g., therapies that involveadministration of a one-time dose drug to a beneficiary), it iscontemplated that the systems, processes, and description providedherein may be applied more generally to the financing of other high costtherapies.

In one aspect, the invention is directed to a method for assessment, bya lender (e.g., a senior lender), of an application for an instrument(e.g., a multi-year structured loan and/or a warranty), and uponapproval, for determination of one or more terms of the instrument, forfinancing one or more of (i), (ii), and (iii) as follows (collectively,the HCT financing): (i) a high cost therapy (HCT) [e.g., a gene or celltherapy (GCT), e.g., said HCT comprising a high-cost treatment, e.g., aGCT drug, e.g., a single or finite dose gene therapy, e.g., a single orfinite dose cellular therapy, e.g., wherein the high cost therapy has acost of at least 100,000 USD, e.g., at least 200,000 USD, e.g., at least300,000 USD] to be administered to a HCT beneficiary (e.g., a personcovered under a health insurance policy, e.g., a health insurance policyof an employer-sponsored health plan, e.g., a health insurance policyprovided by a self-insured employer group (SIEG) or its agent) [e.g.,wherein the financing of the HCT comprises one or more of an upfrontdraw (e.g., a first senior unsecured term loan), a second draw (e.g., asecond senior unsecured term loan), and a holdback amount (e.g., anamount made available to a borrower by a manufacturer of the HCT)], (ii)bundled expenses for pre- and/or post-therapy therapeutic treatmentsand/or services rendered to the HCT beneficiary related to an underlyingmedical condition of the HCT beneficiary addressed by the HCT, and/ormonitoring and/or analysis of the efficacy of the HCT administered tothe HCT beneficiary [e.g., wherein the financing of the bundled expensescomprises a delayed draw], and (iii) an associated performance-basedguaranty of the (e.g., at least initial) efficacy of the HCTadministered to the HCT beneficiary [e.g., said guaranty in the form ofa warranty or other value based agreement (VBA)], wherein saidinstrument is structured in a manner to facilitate portability (e.g.,transferability) of said instrument (e.g., transfer of liability fromthe borrower to a subsequent payer) over the tenor of the instrument,the method comprising: (a) receiving (e.g., by a processor of acomputing platform of the lender) a first set of data of the applicationfor the instrument, said application having been transmitted to thelender by a borrower (e.g., the SIEG or its agent); and (b) determining(e.g., by the processor) whether the instrument is approved using thefirst set of data and/or (e.g., upon approval) determining [e.g., by theprocessor, e.g., said processor utilizing stochastic and/or algorithmicand/or machine learning (and/or other forms of artificial intelligence(AI)) methodologies] a structure (e.g., one or more terms) of theinstrument such that one or more of (i) to (vi) applies, as follows: (i)said HCT financing comprises an upfront draw paid to a party [e.g., aspecialty pharmacy; e.g., a treatment facility (hospital, outpatientclinic); e.g., a pharmaceutical manufacturer] that provides and/oradministers the HCT to the HCT beneficiary [e.g., wherein said upfrontdraw is at least 30% (e.g., at least 40%, at least 50%, at least 60%, atleast 70%, or about 77%) of the cost of the HCT (e.g., plusprocedure-related costs and/or VBA premium cost and/or initial outcomesbenefit administrator (OBA) fee and/or pre-therapeutic bundled expensesand/or an arrangement fee)] and is made at or near the time ofadministration of the HCT to the HCT beneficiary (e.g., just prior to orafter the therapy); (ii) said HCT financing comprises a premium paymentfor a value based agreement (VBA) (e.g., a performance agreement, awarranty, or other insurance product) structured as a performanceguaranty of initial efficacy of the HCT for the HCT beneficiary [e.g.,wherein said initial efficacy is determined using predefined,measurable, reproducible and/or verifiable criteria (e.g., serumbiomarkers, functional tests, etc.), e.g., wherein said criteria areagreed to by both the manufacturer of the HCT (e.g., the manufacturer ofthe GCT drug) and the lender or an identified outcomes benefitadministrator (OBA) in advance of administration of the therapy (e.g.,the GCT drug) to the HCT beneficiary]; (iii) said HCT financingcomprises a second draw paid within an agreed-upon period of time afteradministration of the HCT and upon determination (e.g., by an identifiedOBA) of initial efficacy of the HCT for the HCT beneficiary [e.g.,wherein said second draw covers the remainder of the cost of the HCT(e.g., plus an estimate of post-therapeutic bundled expenses and/oranticipated remaining outcomes benefit administrator (OBA) fees), orcovers said remainder minus a manufacturer's holdback amount (e.g.,5-25%, e.g., 10%, of the cost of the HCT)]; (iv) said HCT financingcomprises bundled expenses for pre- and/or post-therapy therapeutictreatments and/or services rendered to the HCT beneficiary related to anunderlying medical condition of the HCT beneficiary addressed by theHCT, and/or monitoring and/or analysis of the efficacy of the HCTadministered to the HCT beneficiary, said bundled expenses beingcompensated for a contractually-defined episode of care, wherein saidepisode of care is a time period associated with the HCT for which abundled payment (e.g., condition-specific capitation) is made (e.g.,wherein said episode of care is contractually defined as a time periodbeginning when the HCT is prescribed to the HCT beneficiary and lastinguntil maturity of the instrument, e.g., the loan and/or the guaranty);(v) said HCT financing comprises a multi-year structured loan having atenor that ends contiguously with a defined episode of care, whereinsaid episode of care is contractually defined to establish apre-existing condition of the HCT beneficiary, thereby facilitatingportability and/or transferability of associated liability from theborrower (e.g., the SIEG or its agent) to another party [e.g., in theevent of (and upon) exit of the policyholder from the borrower's healthplan (e.g., and upon subsequent entry of the (now former) policyholderunder a new health plan covering the HCT beneficiary)] while the HCTbeneficiary is considered to have the pre-existing condition; and (vi)said HCT financing comprises a value based agreement (e.g., aperformance agreement, a warranty, or other insurance product) having aperiod (e.g., warranty period) that ends contiguously with a definedepisode of care, wherein said episode of care is contractually definedto establish a pre-existing condition of the HCT beneficiary, therebyfacilitating portability and/or transferability of associated liability[e.g., in the event of (and upon) exit of the policyholder from theborrower's health plan (e.g., and upon subsequent entry of the (nowformer) policyholder under a new health plan covering the HCTbeneficiary)] while the HCT beneficiary is considered to have thepre-existing condition.

In certain embodiments, the method further comprises: (c) identifying(e.g., by the processor, e.g., automatically identifying, by theprocessor of the computing platform) a bundle of HCT loans (e.g.,including the loan of the HCT financing of claim 1) to include in asecuritization basket and determining (e.g., by the processor) one ormore terms (e.g., a credit rating, average coupon, position sizing,tranching etc.) of the securitization basket (e.g., thereby providing amechanism to offboard risk to a broader market and/or to facilitatepotentially lower interest rates for individual loans to borrowers,e.g., SIEGs).

In certain embodiments, the high-cost initial treatment is a drug (e.g.,GCT drug) having a National Drug Code (NDC) that identifies mechanism ofpayment via the HCT financing (e.g., wherein said NDC denotes drugpackaging that links to said mechanism of payment).

In certain embodiments, step (b) comprises determining (e.g., by theprocessor) the structure of the instrument, wherein the instrument is amulti-year structured loan having a tenor that matches said episode ofcare, and wherein the loan comprises: an upfront draw to be paid uponadministration of the high-cost initial treatment to the HCT beneficiary(e.g., wherein the upfront draw is an amount in a range from 50% to 90%of the cost of the initial treatment which may or may not includeassociated services that follow such initial treatment that are bundledtogether with the cost of the initial treatment), and a second,subsequent payment to be made upon a final close of the loan followingand contingent upon a determination of initial efficacy of the HCT forthe HCT beneficiary.

In certain embodiments, the final close is in an amount that covers theremainder of the cost of the HCT, which may or may not include theassociated services, less a holdback (e.g., 5%-25%, e.g., 10% of thecost of the HCT) to be paid by borrower to the manufacturer of the highcost initial treatment, e.g., at maturity of the loan. In certainembodiments, the loan comprises a senior tranche amortization period,and wherein the holdback is subordinate to the senior tranche (e.g., theholdback is paid only when the senior tranche is paid in full).

In certain embodiments, the warranty pays off the upfront draw (e.g.,plus a prepayment penalty) upon a determination of initial non-efficacyof the initial treatment in the HCT beneficiary.

In certain embodiments, step (b) comprises determining (e.g., by theprocessor) a structure (e.g., one or more terms) of the instrument ofthe HCT financing based on one or more of the following: total cost ofthe HCT (e.g., exclusive or inclusive of service and administrationcosts); credit rating of the borrower; current debt service of theborrower; assessment of ability of the borrowing firm to collateralizethe loan; assessment of financial solvency and cash flow generatingcapability of the borrowing firm; assessment of desire of themanufacturer to provide subvention; amount, if any, of manufacturerholdback; projected efficacy of the HCT; nature, cost and terms of anassociated warranty; duration of the warranty; the existence, if any,and cost of a current, non-HCT or HCT standard of care therapy; level ofinterest rate benchmarks such as LIBOR (London Interbank Offered Rate)for variable rate loans; prevailing market interest rates for loans ofsimilar tenor and risk profile; market-wide default rates; existence, ifany, of prepayment penalties; and size of any upfront draws.

In another aspect, the invention is directed to a packagedpharmaceutical composition [[alternatively, a kit]] comprising apharmaceutically acceptable vessel, a therapeutic agent secured[[alternatively, sealed]] within the vessel, and a label[[alternatively, package label or vessel label]] [e.g., wherein thepharmaceutically acceptable vessel comprises a vial (e.g., a cryovial orother vial), tube (e.g., a test tube or other tube), multi-well plate,ampule, bottle, bag, box, pouch, patch, syringe, blister pack, strippack, sealed foil, cell culture bag, intravenous (IV) solution bag,cryobag, vitrification straw, drug delivery device, or otherpharmaceutically acceptable vessel known in the art], wherein thetherapeutic agent comprises a high cost therapy drug (a HCT drug), andthe label comprises a description and/or code (e.g., NDC) thatidentifies (e.g., a code that is linked to a description of) how the HCTdrug is financed (e.g., the HCT financing).

In certain embodiments, the description on the label indicates one ormore of (i) to (vi) is applicable to said HCT financing, as follows: (i)said HCT financing comprises an upfront draw paid to a party [e.g., aspecialty pharmacy; e.g., a treatment facility (hospital, outpatientclinic); e.g., a pharmaceutical manufacturer] that provides and/oradministers the HCT to the HCT beneficiary [e.g., wherein said upfrontdraw is at least 30% (e.g., at least 40%, at least 50%, at least 60%, atleast 70%, or about 77%) of the cost of the HCT (e.g., plusprocedure-related costs and/or VBA premium cost and/or initial outcomesbenefit administrator (OBA) fee and/or pre-therapeutic bundled expensesand/or an arrangement fee)] and is made at or near the time ofadministration of the HCT to the HCT beneficiary (e.g., just prior to orafter the therapy); (ii) said HCT financing comprises a premium paymentfor a value based agreement (VBA) (e.g., a performance agreement, awarranty, or other insurance product) structured as a performanceguaranty of initial efficacy of the HCT for the HCT beneficiary [e.g.,wherein said initial efficacy is determined using predefined,measurable, reproducible and/or verifiable criteria (e.g., serumbiomarkers, functional tests, etc.), e.g., wherein said criteria areagreed to by both the manufacturer of the HCT (e.g., the manufacturer ofthe GCT drug) and the lender or an identified outcomes benefitadministrator (OBA) in advance of administration of the therapy (e.g.,the GCT drug) to the HCT beneficiary]; (iii) said HCT financingcomprises a second draw paid within an agreed-upon period of time afteradministration of the HCT and upon determination (e.g., by an identifiedOBA) of initial efficacy of the HCT for the HCT beneficiary [e.g.,wherein said second draw covers the remainder of the cost of the HCT(e.g., plus an estimate of post-therapeutic bundled expenses and/oranticipated remaining outcomes benefit administrator (OBA) fees), orcovers said remainder minus a manufacturer's holdback amount (e.g.,5-25%, e.g., 10%, of the cost of the HCT)]; (iv) said HCT financingcomprises bundled expenses for pre- and/or post-therapy therapeutictreatments and/or services rendered to the HCT beneficiary related to anunderlying medical condition of the HCT beneficiary addressed by theHCT, and/or monitoring and/or analysis of the efficacy of the HCTadministered to the HCT beneficiary, said bundled expenses beingcompensated for a contractually-defined episode of care, wherein saidepisode of care is a time period associated with the HCT for which abundled payment (e.g., condition-specific capitation) is made (e.g.,wherein said episode of care is contractually defined as a time periodbeginning when the HCT is prescribed to the HCT beneficiary and lastinguntil maturity of the instrument, e.g., the loan and/or the guaranty);(v) said HCT financing comprises a multi-year structured loan having atenor that ends contiguously with a defined episode of care, whereinsaid episode of care is contractually defined to establish apre-existing condition of the HCT beneficiary, thereby facilitatingportability and/or transferability of associated liability from theborrower (e.g., an SIEG or its agent) to another party [e.g., in theevent of (and upon) exit of the policyholder from the borrower's healthplan (e.g., and upon subsequent entry of the (now former) policyholderunder a new health plan covering the HCT beneficiary)] while the HCTbeneficiary is considered to have the pre-existing condition; and (vi)said HCT financing comprises a value based agreement (e.g., aperformance agreement, a warranty, or other insurance product) having aperiod (e.g., warranty period) that ends contiguously with a definedepisode of care, wherein said episode of care is contractually definedto establish a pre-existing condition of the HCT beneficiary, therebyfacilitating portability and/or transferability of associated liability[e.g., in the event of (and upon) exit of the policyholder from theborrower's health plan (e.g., and upon subsequent entry of the (nowformer) policyholder under a new health plan covering the HCTbeneficiary)] while the HCT beneficiary is considered to have thepre-existing condition.

In certain embodiments, the drug is a gene or cell therapy drug (GCTdrug).

In certain embodiments, the drug is a single or finite dose gene and/orcellular therapy.

In certain embodiments, the drug comprises one or more members selectedfrom the group consisting of: a biologic drug, a small molecule drug, agene therapy, and a cell therapy (e.g., CAR T-cell therapy). In certainembodiments, the drug comprises one or more members selected from thegroup consisting of: an excipient or other pharmaceutically acceptablecarrier,

In certain embodiments, the pharmaceutically acceptable vessel containsa unit dose of the therapeutic agent.

In one or more additional aspects, the invention is directed to a systemfor assessment of an application for an instrument (e.g., a loan and/ora warranty), and upon approval, for determination of one or more termsof the instrument that forms part of an HCT financing, the systemcomprising: a processor of a computing device (e.g., an enterprisesystem); and a memory having instructions stored thereon, wherein theinstructions, when executed by the processor, cause the processor toperform the method of any one of the aspects and embodiments describedherein.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, aspects, features, and advantages ofthe present disclosure will become more apparent and better understoodby referring to the following description taken in conjunction with theaccompanying drawings, in which:

FIG. 1 is a block flow diagram showing the process for financing of aHCT drug administered to a HCT beneficiary, according to an illustrativeembodiment.

FIG. 2 is a flow diagram of the structure and terms of a loan in thefinancing of a HCT, according to an illustrative embodiment.

FIG. 2A is an illustrative example of a first scenario, according toaspects of the present embodiments.

FIG. 2B is an illustrative example of a second scenario, according toaspects of the present embodiments.

FIG. 2C is an illustrative example of a third scenario, according toaspects of the present embodiments.

FIG. 3 is a block flow diagram of a method for financing a HCT,according to an illustrative embodiment.

FIG. 4 is a block diagram of an exemplary cloud computing environment,used in certain embodiments.

FIG. 5 is a block diagram of an example computing device and an examplemobile computing device used in certain embodiments.

FIG. 6 is a schematic of a packaged pharmaceutical composition,according to an illustrative embodiment.

The features and advantages of the present disclosure will become moreapparent from the detailed description set forth below when taken inconjunction with the drawings, in which like reference charactersidentify corresponding elements throughout. In the drawings, likereference numbers generally indicate identical, functionally similar,and/or structurally similar elements.

Definitions

Agent: As used herein, the term “agent” may refer to any chemicalentity, including without limitation any of one or more of an atom,molecule, compound, amino acid, polypeptide, nucleotide, nucleic acid,protein, protein complex, liquid, solution, saccharide, polysaccharide,lipid, or combination or complex thereof.

Antibody: As used herein, the term “antibody” refers to a polypeptidethat includes one or more canonical immunoglobulin sequence elementssufficient to confer specific binding to a particular antigen (e.g., aheavy chain variable domain, a light chain variable domain, and/or oneor more CDRs). Thus, the term antibody includes, without limitation,human antibodies, non-human antibodies, synthetic and/or engineeredantibodies, fragments thereof, and agents including the same. Antibodiescan be naturally occurring immunoglobulins (e.g., generated by anorganism reacting to an antigen). Synthetic, non-naturally occurring, orengineered antibodies can be produced by recombinant engineering,chemical synthesis, or other artificial systems or methodologies knownto those of skill in the art.

As is known in the art, typical human immunoglobulins are approximately150 kD tetrameric agents that include two identical heavy (H) chainpolypeptides (about 50 kD each) and two identical light (L) chainpolypeptides (about 25 kD each) that associate with each other to form astructure commonly referred to as a “Y-shaped” structure. Typically,each heavy chain includes a heavy chain variable domain (VH) and a heavychain constant domain (CH). The heavy chain constant domain includesthree CH domains: CH1, CH2 and CH3. A short region, known as the“switch”, connects the heavy chain variable and constant regions. The“hinge” connects CH2 and CH3 domains to the rest of the immunoglobulin.Each light chain includes a light chain variable domain (VL) and a lightchain constant domain (CL), separated from one another by another“switch.” Each variable domain contains three hypervariable loops knownas “complement determining regions” (CDR1, CDR2, and CDR3) and foursomewhat invariant “framework” regions (FR1, FR2, FR3, and FR4). In eachVH and VL, the three CDRs and four FRs are arranged from amino-terminusto carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3,CDR3, and FR4. The variable regions of a heavy and/or a light chain aretypically understood to provide a binding moiety that can interact withan antigen. Constant domains can mediate binding of an antibody tovarious immune system cells (e.g., effector cells and/or cells thatmediate cytotoxicity), receptors, and elements of the complement system.Heavy and light chains are linked to one another by a single disulfidebond, and two other disulfide bonds connect the heavy chain hingeregions to one another, so that the dimers are connected to one anotherand the tetramer is formed. When natural immunoglobulins fold, the FRregions form the beta sheets that provide the structural framework forthe domains, and the CDR loop regions from both the heavy and lightchains are brought together in three-dimensional space so that theycreate a single hypervariable antigen binding site located at the tip ofthe Y structure.

In some embodiments, an antibody is a polyclonal, monoclonal,monospecific, or multispecific antibody (e.g., a bispecific antibody).In some embodiments, an antibody includes at least one light chainmonomer or dimer, at least one heavy chain monomer or dimer, at leastone heavy chain-light chain dimer, or a tetramer that includes two heavychain monomers and two light chain monomers. Moreover, the term“antibody” can include (unless otherwise stated or clear from context)any art-known constructs or formats utilizing antibody structural and/orfunctional features including without limitation intrabodies, domainantibodies, antibody mimetics, Zybodies®, Fab fragments, Fab′ fragments,F(ab′)2 fragments, Fd′ fragments, Fd fragments, isolated CDRs or setsthereof, single chain antibodies, single-chain Fvs (scFvs),disulfide-linked Fvs (sdFv), polypeptide-Fc fusions, single domainantibodies (e.g., shark single domain antibodies such as IgNAR orfragments thereof), cameloid antibodies, camelized antibodies, maskedantibodies (e.g., Probodies®), affybodies, anti-idiotypic (anti-Id)antibodies (including, e.g., anti-anti-Id antibodies), Small ModularImmunoPharmaceuticals (“SMIPs™”), single chain or Tandem diabodies(TandAb®), VHHs, Anticalins®, Nanobodies® minibodies, BiTE®s, ankyrinrepeat proteins or DARPINs®, Avimers®, DARTs, TCR-like antibodies,Adnectins®, Affilins®, Trans-bodies®, Affibodies®, TrimerX®,MicroProteins, Fynomers®, Centyrins®, and KALBITOR®s, CARs, engineeredTCRs, and antigen-binding fragments of any of the above.

In various embodiments, an antibody includes one or more structuralelements recognized by those skilled in the art as a complementaritydetermining region (CDR) or variable domain. In some embodiments, anantibody can be a covalently modified (“conjugated”) antibody (e.g., anantibody that includes a polypeptide including one or more canonicalimmunoglobulin sequence elements sufficient to confer specific bindingto a particular antigen, where the polypeptide is covalently linked withone or more of a therapeutic agent, a detectable moiety, anotherpolypeptide, a glycan, or a polyethylene glycol molecule). In someembodiments, antibody sequence elements are humanized, primatized,chimeric, etc, as is known in the art.

An antibody including a heavy chain constant domain can be, withoutlimitation, an antibody of any known class, including but not limitedto, IgA, secretory IgA, IgG, IgE and IgM, based on heavy chain constantdomain amino acid sequence (e.g., alpha (α), delta (δ), epsilon (ε),gamma (γ) and mu (μ). IgG subclasses are also well known to those in theart and include but are not limited to human IgG1, IgG2, IgG3 and IgG4.“Isotype” refers to the Ab class or subclass (e.g., IgM or IgG1) that isencoded by the heavy chain constant region genes. As used herein, a“light chain” can be of a distinct type, e.g., kappa (κ) or lambda (λ),based on the amino acid sequence of the light chain constant domain. Insome embodiments, an antibody has constant region sequences that arecharacteristic of mouse, rabbit, primate, or human immunoglobulins.Naturally-produced immunoglobulins are glycosylated, typically on theCH2 domain. As is known in the art, affinity and/or other bindingattributes of Fc regions for Fc receptors can be modulated throughglycosylation or other modification. In some embodiments, an antibodymay lack a covalent modification (e.g., attachment of a glycan) that itwould have if produced naturally. In some embodiments, antibodiesproduced and/or utilized in accordance with the present inventioninclude glycosylated Fc domains, including Fc domains with modified orengineered such glycosylation.

Antibody fragment: As used herein, an “antibody fragment” refers to aportion of an antibody as described herein, and typically refers to aportion that includes an antigen-binding portion or variable regionthereof. An antibody fragment can be produced by any means. For example,in some embodiments, an antibody fragment can be enzymatically orchemically produced by fragmentation of an intact antibody.Alternatively, in some embodiments, an antibody fragment can berecombinantly produced (i.e., by expression of an engineered nucleicacid sequence. In some embodiments, an antibody fragment can be whollyor partially synthetically produced. In some embodiments, an antibodyfragment (particularly an antigen-binding antibody fragment) can have alength of at least about 50, 60, 70, 80, 90, 100, 110, 120, 130, 140,150, 160, 170, 180, 190 amino acids or more, in some embodiments atleast about 200 amino acids.

Biologic drug or biological product: As used herein, the terms “biologicdrug” or “biological product” refers to a therapeutic agent that is orincludes one or more of a virus, antibody, antibody fragment, nucleicacid (e.g., DNA or RNA), polypeptide, vaccine, cell, bodily fluid (e.g.,blood), bodily fluid component, serum, allergenic agent, toxin,antitoxin, and/or a trivalent organic arsenic compound, and/or analogousproducts and derivatives thereof. In various embodiments, a biologicdrug can be produced according to a process that includes a virus orliving cell. In certain embodiments, a unit dose of a biologic drug canbe characterized in that the unit dose can include molecules of thebiological drug that are non-identical, e.g., that include slightvariation resulting from the process of production. In variousembodiments, a biologic drug can be synthesized, e.g., chemicallysynthesized and/or synthesized without use of a virus or cell. Invarious embodiments, a biologic drug is not a small molecule. In certainparticular embodiments, a biologic drug or biological product means avirus, therapeutic serum, toxin, antitoxin, vaccine, blood, bloodcomponent or derivative, allergenic product, protein, or analogousproduct, or arsphenamine or derivative of arsphenamine (or any othertrivalent organic arsenic compound), applicable to the prevention,treatment, or cure of a disease or condition of human beings.

CAR T-cell or CAR-T therapy: As used herein “CAR T-cell therapy” or“CAR-T therapy” refers to the use of T cells (autologous or allogeneic)engineered with chimeric antigen receptors (CARs, also known as chimericimmunoreceptors, chimeric T cell receptors, or artificial T cellreceptors) as a therapeutic agent in the treatment of a disease, forexample, cancer.

Excipient: As used herein, “excipient” refers to a non-therapeutic agentthat may be included in a pharmaceutical composition, for example toprovide or contribute to a desired consistency or stabilizing effect. Insome embodiments, suitable pharmaceutical excipients may include, forexample, starch, glucose, lactose, sucrose, gelatin, malt, rice, flour,chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodiumchloride, dried skim milk, glycerol, propylene, glycol, water, ethanol,or the like.

Gene therapy: As used herein, the term “gene therapy” refers to theintroduction of genetic material into cells to make a beneficial proteinand/or otherwise compensate for abnormal genes, for example, in thetreatment of a genetic disorder. The genetic material may be introducedinto cells of a subject, for example, using a viral vector, naked DNA,or other technique. In certain embodiments, the expression of the geneis suppressed. In certain embodiments, the expression of the gene isenhanced. In certain embodiments, the temporal or spatial pattern of theexpression of the gene is modulated.

Naked DNA: As used herein, the term “naked DNA” refers to DNA that isnot associated with proteins, lipids, or other molecules to protect it.Administration of naked DNA to a subject (e.g., via intramuscularinjection) has been used in gene therapy as a non-viral transfectionmethod.

Nucleic acid: As used herein, in its broadest sense, the term “nucleicacid” refers to any compound and/or substance that is, or can beincorporated into, an oligonucleotide chain. In some embodiments, theterm nucleic acid refers to an individual nucleic acid residue (e.g., anucleotide and/or nucleoside), and in some embodiments refers to anpolynucleotide chain including a plurality of individual nucleic acidresidues. A nucleic acid can be or include genetic material, forexample, DNA, RNA, or a combinations thereof. A nucleic acid can includenatural nucleic acid residues, nucleic acid analogs, and/or syntheticresidues. In some embodiments, a nucleic acid includes naturalnucleotides (e.g., adenosine, thymidine, guanosine, cytidine, and/oruridine). In some embodiments, a nucleic acid is or includes of one ormore nucleotide analogs (e.g., 2-aminoadenosine, 2-thiothymidine,inosine, pyrrolo-pyrimidine, 3-methyl adenosine, 5-methylcytidine, C-5propynyl-cytidine, C-5 propynyl-uridine, 2-aminoadenosine,C5-bromouridine, C5-fluorouridine, C5-iodouridine, C5-propynyl-uridine,C5-propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine,7-deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8-oxoguanosine,0(6)-methylguanine, 2-thiocytidine, methylated bases, intercalatedbases, and combinations thereof). In some embodiments, a nucleic acidhas a nucleotide sequence that encodes a functional gene product such asan RNA or polypeptide. In some embodiments, a nucleic acid includes oneor more introns. In some embodiments, a nucleic acid includes one ormore genes. In some embodiments, nucleic acids are prepared by one ormore of isolation from a natural source, enzymatic synthesis bypolymerization based on a complementary template (in vivo or in vitro),reproduction in a recombinant cell or system, and chemical synthesis. Insome embodiments, a nucleic acid analog differs from a nucleic acid inthat it does not utilize a phosphodiester backbone. For example, in someembodiments, a nucleic acid can include one or more peptide nucleicacids, which are known in the art and have peptide bonds instead ofphosphodiester bonds in the backbone. Alternatively or additionally, insome embodiments, a nucleic acid has one or more phosphorothioate and/or5′-N-phosphoramidite linkages rather than phosphodiester bonds. In someembodiments, a nucleic acid includes one or more modified sugars (e.g.,2′-fluororibose, ribose, 2′-deoxyribose, arabinose, and hexose) ascompared with natural nucleic acids. In some embodiments, a nucleic acidcan include at least 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40,45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300,400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000,4500, 5000 or more residues. In some embodiments, a nucleic acid ispartly or wholly single stranded, or partly or wholly double stranded.In some embodiments, a nucleic acid has enzymatic activity.

Pharmaceutically acceptable: As used herein, the term “pharmaceuticallyacceptable,” as applied to one or more, or all, component(s) of acomposition as disclosed herein, means that each component must becompatible with the other components of the composition and notdeleterious to a recipient thereof.

Pharmaceutically acceptable carrier: As used herein, the term“pharmaceutically acceptable carrier” refers to apharmaceutically-acceptable material, composition, or vehicle, such as aliquid or solid filler, diluent, excipient, or solvent encapsulatingmaterial, that facilitates formulation of an agent (e.g., apharmaceutical agent), modifies bioavailability of an agent, orfacilitates transport of an agent from one organ or portion of a subjectto another. Some examples of materials which can serve aspharmaceutically-acceptable carriers include: sugars, such as lactose,glucose and sucrose; starches, such as corn starch and potato starch;cellulose, and its derivatives, such as sodium carboxymethyl cellulose,ethyl cellulose and cellulose acetate; powdered tragacanth; malt;gelatin; talc; excipients, such as cocoa butter and suppository waxes;oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil,olive oil, corn oil and soybean oil; glycols, such as propylene glycol;polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol;esters, such as ethyl oleate and ethyl laurate; agar; buffering agents,such as magnesium hydroxide and aluminum hydroxide; alginic acid;pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol;pH buffered solutions; polyesters, polycarbonates and/or polyanhydrides;and other non-toxic compatible substances employed in pharmaceuticalformulations.

Pharmaceutical composition, formulation, or drug: As used herein, theterm “pharmaceutical composition” or “formulation” or “drug” refers to acomposition in which a therapeutic agent is formulated together with oneor more pharmaceutically acceptable carriers.

Polypeptide: As used herein, “polypeptide” refers to any polymeric chainof amino acids. In some embodiments, a polypeptide has an amino acidsequence that occurs in nature. In some embodiments, a polypeptide hasan amino acid sequence that does not occur in nature. In someembodiments, a polypeptide has an amino acid sequence that is engineeredin that it is designed and/or produced through action of the hand ofman. In some embodiments, a polypeptide can include one or both ofnatural amino acids and non-natural amino acids. In some embodiments, apolypeptide can include D-amino acids, L-amino acids, or both. In someembodiments, a polypeptide may include only L-amino acids. In someembodiments, a polypeptide may include one or more pendant groups orother modifications, e.g., one or more amino acid side chains, e.g., atthe polypeptide's N-terminus, at the polypeptide's C-terminus, atnon-terminal amino acids, or at any combination thereof. In someembodiments, such pendant groups or modifications may be selected fromacetylation, amidation, lipidation, methylation, phosphorylation,glycosylation, glycation, sulfation, mannosylation, nitrosylation,acylation, palmitoylation, prenylation, pegylation, etc., includingcombinations thereof. In some embodiments, a polypeptide may be cyclic,and/or may include a cyclic portion. In some embodiments, a polypeptidecan include at least 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40,45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300 ormore residues.

Small molecule: As used herein, the term “small molecule” means a lowmolecular weight organic and/or inorganic compound. As used herein, theterm “small molecule drug” is a drug whose active agent comprises asmall molecule. In general, a “small molecule” is a molecule that isless than about 5 kilodaltons (kD) in size. In some embodiments, a smallmolecule is less than about 4 kD, 3 kD, about 2 kD, or about 1 kD. Insome embodiments, the small molecule is less than about 800 daltons (D),about 600 D, about 500 D, about 400 D, about 300 D, about 200 D, orabout 100 D. In some embodiments, a small molecule is less than about2000 g/mol, less than about 1500 g/mol, less than about 1000 g/mol, lessthan about 800 g/mol, or less than about 500 g/mol. In some embodiments,a small molecule is not a polymer. In some embodiments, a small moleculedoes not include a polymeric moiety. In some embodiments, a smallmolecule is not and/or does not include a protein or polypeptide (e.g.,is not an oligopeptide or peptide). In some embodiments, a smallmolecule is not and/or does not include a polynucleotide (e.g., is notan oligonucleotide). In some embodiments, a small molecule is not and/ordoes not include a polysaccharide; for example, in some embodiments, asmall molecule is not a glycoprotein, proteoglycan, glycolipid, etc.).In some embodiments, a small molecule is not a lipid. In someembodiments, a small molecule is a modulating agent (e.g., is aninhibiting agent or an activating agent). In some embodiments, a smallmolecule is biologically active. In some embodiments, a small moleculeis detectable (e.g., includes at least one detectable moiety). In someembodiments, a small molecule is a therapeutic agent. Those of ordinaryskill in the art, reading the present disclosure, will appreciate thatcertain small molecule compounds described herein may be provided and/orutilized in any of a variety of forms such as, for example, crystalforms, salt forms, protected forms, pro-drug forms, ester forms,isomeric forms (e.g., optical and/or structural isomers), isotopicforms, etc. Those of skill in the art will appreciate that certain smallmolecule compounds have structures that can exist in one or moresteroisomeric forms. In some embodiments, such a small molecule may beutilized in accordance with the present disclosure in the form of anindividual enantiomer, diastereomer or geometric isomer, or may be inthe form of a mixture of stereoisomers; in some embodiments, such asmall molecule may be utilized in accordance with the present disclosurein a racemic mixture form. Those of skill in the art will appreciatethat certain small molecule compounds have structures that can exist inone or more tautomeric forms. In some embodiments, such a small moleculemay be utilized in accordance with the present disclosure in the form ofan individual tautomer, or in a form that interconverts betweentautomeric forms. In some embodiments, reference to a particular smallmolecule compound may relate to a specific form of that compound. Insome embodiments, a particular small molecule compound may be providedand/or utilized in a salt form (e.g., in an acid-addition orbase-addition salt form, depending on the compound); in some suchembodiments, the salt form may be a pharmaceutically acceptable saltform. In some embodiments, where a small molecule compound is one thatexists or is found in nature, that compound may be provided and/orutilized in accordance in the present disclosure in a form differentfrom that in which it exists or is found in nature. Those of ordinaryskill in the art will appreciate that, in some embodiments, apreparation of a particular small molecule compound that contains anabsolute or relative amount of the compound, or of a particular formthereof, that is different from the absolute or relative (with respectto another component of the preparation including, for example, anotherform of the compound) amount of the compound or form that is present ina reference preparation of interest (e.g., in a primary sample from asource of interest such as a biological or environmental source) isdistinct from the compound as it exists in the reference preparation orsource.

Therapeutic agent or drug: As used herein, the term “therapeutic agent”or “drug” refers to any agent that elicits a desired pharmacologicaleffect when administered to a subject. In some embodiments, an agent isconsidered to be a therapeutic agent if it demonstrates a statisticallysignificant effect across an appropriate population. In someembodiments, the appropriate population can be a population of modelorganisms or a human population. In some embodiments, an appropriatepopulation can be defined by various criteria, such as a certain agegroup, gender, genetic background, preexisting clinical conditions, etc.In some embodiments, a therapeutic agent is a substance that can be usedfor treatment of a disease, disorder, or condition. In some embodiments,a therapeutic agent is an agent that has been or is required to beapproved by a government agency before it can be marketed foradministration to humans. In some embodiments, a therapeutic agent is anagent for which a medical prescription is required for administration tohumans.

Unit dose: As used herein, the term “unit dose” refers to an amountadministered as a single dose and/or in a physically discrete unit of apharmaceutical composition. In many embodiments, a unit dose contains apredetermined quantity of an therapeutic agent. In some embodiments, aunit dose contains an entire single dose of the agent. In someembodiments, more than one unit dose is administered to achieve a totalsingle dose. In some embodiments, administration of multiple unit dosesis required, or expected to be required, in order to achieve an intendedeffect. A unit dose can be, for example, a volume of liquid (e.g., anacceptable carrier) containing a predetermined quantity of one or moretherapeutic agents, a predetermined amount of one or more therapeuticagents in solid form, a sustained release formulation or drug deliverydevice containing a predetermined amount of one or more therapeuticagents, etc. It will be appreciated that a unit dose can be present in aformulation that includes any of a variety of components in addition tothe therapeutic agent(s). For example, acceptable carriers (e.g.,pharmaceutically acceptable carriers), diluents, stabilizers, buffers,preservatives, etc., can be included. It will be appreciated by thoseskilled in the art that, in many embodiments, a total appropriate dailydosage of a particular therapeutic agent can include a portion, or aplurality, of unit doses, and can be decided, for example, by a medicalpractitioner within the scope of sound medical judgment. In someembodiments, the specific effective dose level for any particularsubject or organism can depend upon a variety of factors including thedisorder being treated and the severity of the disorder; activity ofspecific therapeutic agent employed; specific composition employed; age,body weight, general health, sex and diet of the subject; time ofadministration, and rate of excretion of the specific therapeutic agentemployed; duration of the treatment; drugs and/or additional therapiesused in combination or coincidental with specific compound(s) employed,and like factors well known in the medical arts.

Vessel: As used herein, in certain embodiments, the term “vessel” refersto a container that is sufficient to contain and/or enclose a singleunit dose. In various embodiments, a vessel can be sufficient to containand/or enclose multiple unit doses. In various embodiments, a vessel canbe a vial (e.g., a cryovial or other vial), tube (e.g., a test tube orother tube), multi-well plate, ampule, bottle, bag, box, pouch, patch,syringe, blister pack, strip pack, sealed foil, cell culture bag,intravenous (IV) solution bag, cryobag, vitrification straw, drugdelivery device, or other pharmaceutically acceptable vessel known inthe art. In various embodiments a vessel can be composed of one or moreof plastic, glass, laminated paper, metal, foil (e.g., a metal foil orplastic foil), or other pharmaceutically acceptable material forcontaining and/or enclosing a pharmaceutical agent. In variousembodiments a vessel contains and/or encloses one or more unit doses ofa pharmaceutical agent. In various embodiments a vessel is empty in thatit does not contain and/or enclose, and/or has not been loaded with, apharmaceutical agent.

Viral vector: As used herein, plasmid or viral vectors are agents thattransport the disclosed nucleic acids (e.g., a therapeutic agent) intothe cell without degradation and include a promoter yielding expressionof the gene in the cells into which it is delivered. In someembodiments, the promoters are derived from either a virus or aretrovirus. Viral vectors are, for example, Adenovirus, Adeno-associatedvirus, Herpes virus, Vaccinia virus, Polio virus, AIDS virus, neuronaltrophic virus, Sindbis and other RNA viruses, including these viruseswith the HIV backbone. Also disclosed are any viral families which sharethe properties of these viruses which make them suitable for use asvectors. Retroviruses include Murine Maloney Leukemia virus, MMLV, andretroviruses that express the desirable properties of MMLV as a vector.Retroviral vectors are able to carry a larger genetic payload, i.e., atransgene or marker gene, than other viral vectors, and for this reasonare a commonly used vector. However, they are not as useful innon-proliferating cells. Adenovirus vectors are relatively stable andeasy to work with, have high titers, and can be delivered in aerosolformulation, and can transfect non-dividing cells. Pox viral vectors arelarge and have several sites for inserting genes, they are thermostableand can be stored at room temperature. Viral vectors can have highertransfection (ability to introduce genes) abilities than chemical orphysical methods to introduce genes into cells. Typically, viral vectorscontain, nonstructural early genes, structural late genes, an RNApolymerase III transcript, inverted terminal repeats necessary forreplication and encapsidation, and promoters to control thetranscription and replication of the viral genome. When engineered asvectors, viruses typically have one or more of the early genes removedand a gene or gene/promotor cassette is inserted into the viral genomein place of the removed viral DNA. Constructs of this type can carry upto about 8 kb of foreign genetic material. The necessary functions ofthe removed early genes are typically supplied by cell lines which havebeen engineered to express the gene products of the early genes intrans.

DETAILED DESCRIPTION

It is contemplated that systems, architectures, devices, methods, andprocesses of the claimed invention encompass variations and adaptationsdeveloped using information from the embodiments described herein.Adaptation and/or modification of the systems, architectures, devices,methods, and processes described herein may be performed, ascontemplated by this description.

Throughout the description, where articles, devices, systems, andarchitectures are described as having, including, or comprising specificcomponents, or where processes and methods are described as having,including, or comprising specific steps, it is contemplated that,additionally, there are articles, devices, systems, and architectures ofthe present invention that consist essentially of, or consist of, therecited components, and that there are processes and methods accordingto the present invention that consist essentially of, or consist of, therecited processing steps.

It should be understood that the order of steps or order for performingcertain action is immaterial so long as the invention remains operable.Moreover, two or more steps or actions may be conducted simultaneously.

The mention herein of any publication, for example, in the Backgroundsection, is not an admission that the publication serves as prior artwith respect to any of the claims presented herein. The Backgroundsection is presented for purposes of clarity and is not meant as adescription of prior art with respect to any claim.

Documents are incorporated herein by reference as noted. Where there isany discrepancy in the meaning of a particular term, the meaningprovided in the Definition section above is controlling.

Headers are provided for the convenience of the reader—the presenceand/or placement of a header is not intended to limit the scope of thesubject matter described herein.

FIG. 1 is a block flow diagram showing an example process 100 forfinancing of a HCT drug administered to a HCT beneficiary, according toan illustrative embodiment. In this example, “Patient” is the HCTbeneficiary, “Specialty Pharmacy” is the entity that receives and fillsthe prescription for the HCT, “Self-Insured Employer Group (SIEG) ortheir agent” is the borrower/payer, “Manufacturer” is the manufacturerof the HCT, and “octaviantFinancial (OFX)” is the lender. In otherembodiments, the borrower/payer may not be a SIEG but rather is astate-backed (or other public) insurance plan, other third party healthinsurance provide, or other third party. Furthermore, in otherembodiments, the tasks of the Specialty Pharmacy are handled by themanufacturer directly, or a distributor, wholesaler, hospital (e.g., a340 b pharmacy), or other third party. At “Start” 102 in the embodimentshown in FIG. 1, the Patient is prescribed a HCT drug 104, which, incertain embodiments, begins the “episode of care”. In other embodiments,the episode of care begins at the execution of the term sheet or loandocuments, or at another point in time decided upon by the lender andkey stakeholders (e.g., the payer, manufacturer, etc.). The SpecialtyPharmacy receives the prescription 106 and transmits a correspondingprescription claim to SIEG 108, who receives it and determines theeligibility of the prescription claim. In this example, SIEG eitherapproves the prescription claim or denies it 110. If SIEG denies theclaim, the process ends 112. If SIEG approves the claim, it determinesif the manufacturer or other party offers a warranty 114. If so, SIEGmay choose to purchase the warranty through the manufacturer 116 (e.g.,a warranty that the drug will be efficacious for the patient). If not,SIEG decides whether or not to pay in full for the drug and/or for thewarranty 118. If SIEG pays for the drug, the specialty pharmacy receivespayment 120 and dispenses the drug to the patient 122, and the processends 124. If SIEG does not pay in full, SIEG applies for financing ofthe drug and/or for the warranty 126. The lender/financing companyevaluates SIEG for financing of the drug and/or the warranty 128. Iffinancing is not approved 130, the SIEG pays the Specialty Pharmacy infull for the drug 132 and the patient receives the drug. If financing isapproved for the SIEG, the financing process is completed through thelender's IT platform 134 (e.g., as described herein) for setting termsof one or more instruments (e.g., loan and/or warranty) in the HCTfinancing. Upon completion, OFX disburses funds 136 and the SpecialtyPharmacy receives payment and dispenses the drug to the patient.Finally, any payments from SIEG (whether one time or regularlyrecurring, e.g., monthly or quarterly) may be managed by a third partyfor the term of the loan 138, whereupon the process 100 ends 140.

FIG. 2 is a flow diagram 200 of the structure and terms of an exampleloan in the financing of a HCT, according to an illustrative embodiment.The size of the loan may range, for example, from about 0.5 million toabout 2.0 million USD, and has a tenor/maturity date, for example, 5years. The use of proceeds is to fund (a) the price of the HCT, (b) avalue-based agreement premium (VBA premium), (c) bundled expenses,defined as approved costs and expenses of pre- or post-therapytherapeutic treatments and services, (d) procedure-related costs, (e)the OBA fee, and (f) an arrangement fee. As referenced in FIG. 2, inthis example, the borrower is the payer of the HCT (current andsubsequent, if applicable), the HCT beneficiary is the individual who isthe recipient of the HCT, and the guarantor is the employer of thepolicyholder of the policy that covers the HCT beneficiary.

In this example, the lender pays an Upfront Draw 202 (e.g., 77% of theHCT Price, e.g., a GCT, e.g., a one-dose or finite-dose drug, plusprocedure-related costs, plus an initial outcomes benefit administrator(OBA) fee, plus the VBA premium, plus the arrangement fee) around thetime of (e.g., immediately before, the day of, or shortly after)administration of the HCT to the HCT beneficiary. In certainembodiments, the Upfront Draw 202 is a percentage of the HCT price(e.g., cost of the drug charged by the manufacturer) plus certainprocedure-related costs and/or the value based agreement premium cost,and/or initial outcomes benefit administrator (OBA) fee and/orpre-therapeutic bundled expenses and/or an arrangement fee. After aDetermination Period 204 has elapsed (e.g., a period of time on theorder of weeks up to several months, depending on the therapy), adetermination is made regarding whether the drug is at least initiallyefficacious for the beneficiary. For example, for a GCT, a determinationis made as to whether the therapy has successfully been transfected intothe patient/beneficiary and/or whether it has generated an adverseresponse which would render the therapy ineffective or undesired. If thedetermination is that the therapy is not efficacious the warranty paysoff the Upfront Draw 202 plus a Prepayment Penalty and the Loan isterminated. If the determination is that the therapy is at leastinitially efficacious for the beneficiary, the lender pays a Second Draw206 (in this example, 13% of the cost of the HCT plus an estimate of thepost-therapeutic bundled expenses, plus anticipated remaining OBA fees)and the Loan is Finalized 210 (e.g., at Final Close 208).

In this example, following an Amortization Period 212, there is aHoldback 214, which is a percentage of the face amount of the Loanfinanced by the manufacturer of the HCT. Terms of the Holdback 214 canbe adjusted keeping in mind that standardization may increase marketacceptance (e.g., target implied interest rate, timing of cash payments,etc.). In certain embodiments, the Holdback 214 is subordinated in rightof payment pursuant to an agreement among the lenders (inclusive of themanufacturer). The Holdback provides two primary functions:subordination to the Senior Tranche (paid by the lender), thus loweringthe required yield on the senior tranche, and a form of subvention bythe manufacturer that can reduce the total interest rate paid by theborrower(s). The size and timing of repayments for the Holdback 214 willbe impacted by certain accounting assumptions that will affect revenuerecognition and cash flows for the manufacturer. The Holdback 214 isinvestor friendly in that it (a) acts as a credit enhancement and (b)demonstrates risk taken on behalf of manufacturers. The Holdback 214 ispaid at loan maturity, assuming the senior tranche is paid in full.

In the illustrative financing of FIG. 2, the Episode of Care is theperiod beginning on the Prescription Date and ending upon maturity ofthe Loan or Value-Based Agreement (VBA) (i.e., Warranty) during whichall services are provided to the beneficiary to treat the medicalcondition, including the HCT, procedure-related costs, and bundledexpenses. In other embodiments, the Episode of Care begins at theexecution of the term sheet or loan documents, or at another point intime decided upon by the lender and key stakeholders (e.g., the payer,manufacturer, etc.). The Episode of Care covers the same time period asa contractually-defined Pre-Existing Condition, which is contractuallydefined as the underlying medical condition necessitating the HCT, whichnecessarily continues during the treatment with the HCT and throughoutthe period during which procedure-related costs and bundled expenses areincurred for the duration of the Episode of Care. The Episode of Careand Pre-Existing Condition facilitate portability for the Loan and/orWarranty. If this structure is incorporated into HCT payment schemes, itis estimated the Total Addressable Market for HCT will increase from$4.8 billion to over $30 billion.

TABLE 1 Certain Definitions Term Definition Size: $[0.5-2.0] millionTenor/Maturity Date: [5] years Coupon: [[Term SOFR/Daily Simple SOFR] +[spread] + TBD % Use of Proceeds: To fund (a) HCT Price, (b) value-basedagreement premium (VBA Premium), (c) Bundled Expenses, defined asapproved costs and expenses of pre- or post-therapy therapeutictreatments and services, (d) Procedure-Related Costs, (e) the OBA fee,and (f) Arrangement Fee Borrower: Payer of the HCT (current andSubsequent, if applicable) HCT Beneficiary: The individual who is therecipient of the HCT Guarantor: Employer of the policyholder at time oftreatment Portability: These specific terms facilitate portability forthe Loan and the VBA Pending industry acceptance, they can beincorporated into all HCT payment schemes, thus increasing TAM (est.)from $4.8 billion to $30+ billion. Upfront Draw: (i) [77]% of the HCTPrice, plus (ii) Procedure-Related Costs, plus (iii) Initial OBA Fee,plus (iv) the VBA Premium, plus (v) pre-therapeutic Bundled Expenses,plus (vi) the Arrangement Fee Second Draw: (i) [13]% of the HCT Price,plus (ii) an estimate of the post- therapeutic Bundled Expenses, plus(iii) anticipated remaining OBA Fees Holdback: [10]% of the HCT Price,deferred payment by Borrow to Manufacturer; subordinated in right ofpayment to the Facilities Determination Period: [TBD] period, duringwhich time indicative efficacy is evaluated Prepayment Penalty: [TBD]%of total outstanding Loans Episode of Care: All services provided to theBeneficiary to treat the medical condition, including the HCT,Procedure-Related Costs and Bundled Expenses, beginning on thePrescription Date and ending on the Maturity Date Pre-Existing ConditionThe Beneficiary's underlying medical condition, which necessarilycontinues during the treatment with the HCT throughout the period duringwhich Procedure-Related Costs and Bundled Expenses are incurred for theduration of the Episode of Care.

Table 1 above includes definitions of certain terminology that is usedin FIG. 2, as well as elsewhere in the present disclosure.

FIGS. 2A, 2B, and 2C illustrate three possible scenarios, according toaspects of the present embodiments. In FIG. 2A, which illustrates afirst scenario that includes a successful treatment, an HCT isprescribed 216 to a patient. Following the prescription 216 of an HCT tothe patient, a collateralized therapeutic obligation (e.g., CTxO™) loanand warranty are established 218 whereby the manufacturer is paid 77% ofthe HCT price. The loan proceeds may also pay for VBA (warranty)premium, pre-treatment bundled expenses, procedure-related costs, theOBA fee, and/or other appropriate expenses. Very soon after thecollateralized therapeutic obligation (e.g., CTxO™) loan and warrantyare established 218 (i.e., almost immediately after), the HCT isadministered 220 to the patient (or beneficiary). Once the HCT isadministered, an initial efficacy determination period 222 is initiated.During the initial efficacy determination period 222, the patient ismonitored to see if 1) the patient's body rejects the treatment, 2) theHCT doesn't take, 3) the HCT doesn't produce one or more expectedproteins, and/or 4) the HCT proves to be otherwise ineffective. Inscenario 1 illustrated in FIG. 2A, the HCT is determined to bepotentially successful 224 by the OBA, at which time the initialefficacy determination period 222 concludes and the payer/borrowerbegins repaying 226 the loan. At the time the HCT is determined to bepotentially successful 224 by the OBA, the manufacturer is paid 13% ofthe HCT price 228. Following the OBA determining the HCT is potentiallysuccessful 224, the patient continues to be monitored 230 by the OBA,and the payer/borrower continues to repay 226 the loan. In scenario 1,eventually, the patient treatment is determined to be successful 232 andthe loan is repaid 234. At this time, the manufacture is paid 236 theremaining 10% of the HCT price.

FIG. 2B illustrates a second scenario in which the treatment isdetermined to be unsuccessful, according to aspects of the presentembodiments. The second scenario is identical to the first scenario upuntil after the OBA determines the HCT to be potentially successful 238.In scenario 2, at some point during the monitoring 240 of the patient bythe OBA, the OBA determines that the patient treatment is unsuccessful242. At this time, patient monitoring is discontinued 244 and theremaining loan balance (or liability) is paid 246 by the warranty.

FIG. 2C illustrates a third scenario in which the treatment isdetermined 248 to be unsuccessful during the initial efficacydetermination period 250, according to aspects of the presentembodiments. In the third scenario, the OBA determines 248 that thetreatment is unsuccessful during the initial efficacy determinationperiod 250 (i.e., prior to the OBA determining the HCT to be potentiallysuccessful). In scenario 3, once the OBA determines 248 the treatment isunsuccessful, the warranty pays 252 upfront payment and prepaymentpenalties, and the loan is terminated.

FIG. 3 is a block flow diagram (300) of a method performed in thefinancing of a HCT, according to an illustrative embodiment. Morespecifically, the block flow diagram (300) illustrates a method forassessment, by a lender (e.g., a senior lender), of an application foran instrument (e.g., a multi-year structured loan and/or a warranty),and upon approval, for determination of one or more terms of theinstrument, for financing one or more of (i), (ii), and (iii) as follows(collectively, the HCT financing): (i) a high cost therapy (HCT) [e.g.,a gene or cell therapy (GCT), e.g., said HCT comprising a high-costtreatment, e.g., a GCT drug, e.g., a single or finite dose gene therapy,e.g., a single or finite dose cellular therapy, e.g., wherein the highcost therapy has a cost of at least 100,000 USD, e.g., at least 200,000USD, e.g., at least 300,000 USD] to be administered to a HCT beneficiary(e.g., a person covered under a health insurance policy, e.g., a healthinsurance policy of an employer-sponsored health plan, e.g., a healthinsurance policy provided by a self-insured employer group (SIEG) or itsagent) [e.g., wherein the financing of the HCT comprises one or more ofan upfront draw (e.g., a first senior unsecured term loan), a seconddraw (e.g., a second senior unsecured term loan), and a holdback amount(e.g., an amount made available to a borrower by a manufacturer of theHCT)], (ii) bundled expenses for pre- and/or post-therapy therapeutictreatments and/or services rendered to the HCT beneficiary related to anunderlying medical condition of the HCT beneficiary addressed by theHCT, and/or monitoring and/or analysis of the efficacy of the HCTadministered to the HCT beneficiary [e.g., wherein the financing of thebundled expenses comprises a delayed draw], and (iii) an associatedperformance-based guaranty of the (e.g., at least initial) efficacy ofthe HCT administered to the HCT beneficiary [e.g., said guaranty in theform of a warranty or other value based agreement (VBA)], wherein theinstrument is structured in a manner to facilitate portability (e.g.,transferability) of said instrument (e.g., transfer of liability fromthe borrower to a subsequent payer) over the tenor of the instrument.

In step 310, the method includes receiving (e.g., by a processor of acomputing platform of the lender) a first set of data of the applicationfor the instrument, said application having been transmitted to thelender by a borrower (e.g., the SIEG or its agent).

In step 320, the method includes determining (e.g., by the processor)whether the instrument is approved using the first set of data and/or(e.g., upon approval) determining [e.g., by the processor e.g., saidprocessor utilizing stochastic and/or algorithmic and/or machinelearning (and/or other forms of artificial intelligence (AI))methodologies] a structure (e.g., one or more terms) of the instrumentsuch that one or more of (i) to (vi) applies, as follows: (i) the HCTfinancing comprises an upfront draw paid to a party [e.g., a specialtypharmacy; e.g., a treatment facility (hospital, outpatient clinic);e.g., a pharmaceutical manufacturer] that provides and/or administersthe HCT to the HCT beneficiary [e.g., wherein said upfront draw is atleast 30% (e.g., at least 40%, at least 50%, at least 60%, at least 70%,or about 77%) of the cost of the HCT (e.g., plus procedure-related costsand/or VBA premium cost and/or initial outcomes benefit administrator(OBA) fee and/or pre-therapeutic bundled expenses and/or an arrangementfee)] and is made at or near the time of administration of the HCT tothe HCT beneficiary (e.g., just prior to or after the therapy); (ii) theHCT financing comprises a premium payment for a value based agreement(e.g., a performance agreement, a warranty, or other insurance product)structured as a performance guaranty of initial efficacy of the HCT forthe HCT beneficiary [e.g., wherein said initial efficacy is determinedusing predefined, measurable, reproducible and/or verifiable criteria(e.g., serum biomarkers, functional tests, etc.), e.g., wherein saidcriteria are agreed to by both the manufacturer of the HCT (e.g., themanufacturer of the GCT drug) and the lender or an outcomes benefitadministrator (OBA) in advance of administration of the therapy (e.g.,the GCT drug) to the HCT beneficiary]; (iii) the HCT financing comprisesa second draw paid within an agreed-upon period of time afteradministration of the HCT and upon determination (e.g., by an identifiedOBA) of initial efficacy of the HCT for the HCT beneficiary [e.g.,wherein said second draw covers the remainder of the cost of the HCT(e.g., plus an estimate of post-therapeutic bundled expenses and/oranticipated remaining outcomes benefit administrator (OBA) fees), orcovers said remainder minus a manufacturer's holdback amount (e.g.,5-25%, e.g., 10%, of the cost of the HCT)]; (iv) the HCT financingcomprises bundled expenses for pre- and/or post-therapy therapeutictreatments and/or services rendered to the HCT beneficiary related to anunderlying medical condition of the HCT beneficiary addressed by theHCT, and/or monitoring and/or analysis of the efficacy of the HCTadministered to the HCT beneficiary, said bundled expenses beingcompensated for a contractually-defined episode of care, wherein saidepisode of care is a time period associated with the HCT for which abundled payment (e.g., condition-specific capitation) is made (e.g.,wherein said episode of care is contractually defined as a time periodbeginning when the HCT is prescribed to the HCT beneficiary and lastinguntil maturity of the instrument, e.g., the loan and/or the guaranty);(v) the HCT financing comprises a multi-year structured loan having atenor that ends contiguously with a defined episode of care, whereinsaid episode of care is contractually defined to establish apre-existing condition of the HCT beneficiary, thereby facilitatingportability and/or transferability of associated liability from theborrower (e.g., the SIEG or its agent) to another party [e.g., in theevent of (and upon) exit of the policyholder from the borrower's healthplan (e.g., and upon subsequent entry of the (now former) policyholderunder a new health plan covering the HCT beneficiary)] while the HCTbeneficiary is considered to have the pre-existing condition; and (vi)the HCT financing comprises a value based agreement (e.g., a performanceagreement, a warranty, or other insurance product) having a period(e.g., warranty period) that ends contiguously with an episode of care,wherein said episode of care is contractually defined to establish apre-existing condition of the HCT beneficiary, thereby facilitatingportability and/or transferability of associated liability [e.g., in theevent of (and upon) exit of the policyholder from the borrower's healthplan (e.g., and upon subsequent entry of the (now former) policyholderunder a new health plan covering the HCT beneficiary)] during the timethe HCT beneficiary is considered to have the pre-existing condition.

FIG. 4 is a block diagram of an exemplary cloud computing environment,used in certain embodiments.

FIG. 5 is a block diagram of an example computing device and an examplemobile computing device used in certain embodiments.

In certain embodiments, algorithms are used to automate the evaluationof risk in issuing a loan to a borrower by estimating an aggregate riskvalue from a set of facts and data about the borrower, where suchevaluation of risk is used as a threshold condition to determine whethera borrower is approved for the loan terms using computer-executableinstructions for causing the computer processor to be configured to: (i)retrieve the total cost of therapy from a third party who may aggregateaverage costs across a diverse network of care providers; and (ii)retrieve borrower credit data, including but not limited to one or moreof the following: the borrower credit rating; prior history of default;current debt service; current capital structure; history of healthcareexpenditures for beneficiary [e.g., whether the borrower is currentlypaying and/or previously paid a high cost therapy standard of care (HCTSOC)]; expenditures of the health plan in general; assets including oneor more of accounts receivables, cash, inventories, prepaid expenses,securities, among others; real estate owned; other assets available toserve as collateral; liabilities such as account payables, notespayables, accrued expenses, short term debt, among others; cash flowincluding the last five years of operating cash flow, cash flow fromfinancing, cash flow from investing, levered and unlevered free cashflow; financial auditing policies and auditors used to present theborrower's corporate finances; number of current employees; wageobligations; and other metrics deemed necessary to establish theborrower's credit risk, wherein one or more factors of the borrowercredit data is used by one or more computer algorithms (e.g., artificialintelligence models) (computer-executable instructions) to determine theborrower aggregated risk value as compared to a threshold condition,where the algorithm outputs to an entity one more data points regardingthe aggregate risk value as compared to a threshold condition.

In certain embodiments, algorithms are used to automate the loan termsusing computer-executable instructions for causing the computer processto be configured to retrieve “Loan Factors”, which may include one ormore of the following: (i) the total cost of care, which may include oneor more of the costs charged by a formulating pharmacy, the cost chargedby the therapeutic manufacturer, a value-based agreement premium, e.g.,which may be a pre-set number retrieved by the executable instructionsor may be a number calculated by the algorithm; (ii) the determinationperiod; (iii) the timing of cost of care over the determination period;(iv) the amount and/or percent of the upfront draw; (v) one or more dataregarding the borrower and/or its credit data; (vi) data regarding themanufacturer preferred loan terms, which may include one or more of thefollowing: amount and/or timing of cash payments, size and/or timing ofholdback terms, or the like; (vii) the stated and/or probabilisticallycalculated efficacy of the GCT; (viii) data on the associated warranty,e.g., including its nature, cost, and/or terms; (ix) prevailing variableinterest rate floors established by benchmarks such as LIBOR; (x)current market interest rates for loans of similar tenor and riskprofile; (xi) market-wide default rates; (xii) pre-determined penaltiesfor pre-payment; and (xiii) aggregate and/or individual risks, whereinthe algorithm calculates the Loan Terms and Loan Structure, andauto-fills an offer term sheet and loan agreement.

In accordance with various aspects of the present disclosure, one ormore of the Loan Factors (upfront draw percent, market interest rate,pre-payment penalties, etc.) and/or Loan Structure may be predefinedand/or may be dynamically adapted by one or more computer systemslocally and/or in a cloud-based system (e.g., any of the computersystems and/or networks described herein). This flexibility enables theprioritization of some Loan Terms and/or Loan Structures over others.

Deidentified clinical data may be supplied by the outcomes-basedadministrator for the purposes of internal analysis. These data may beused to statistically assess the continued durability of the GCT in thecurrent beneficiary or for future efficacy and durability assessments offuture beneficiaries receiving the same GCT. The data may also be usedto assess patient compliance with the follow-up protocol as stipulatedin the warranty and as agreed to by the manufacturer and the payer. Inaccordance with various aspects of the present disclosure, the efficacyof the GCT is saved for each loan and the patient profile, which may beone or more characteristics of the employee received by the lender, suchas physical characteristics, age, genome sequence (full or partial),known medical history including date of diagnosis, among others. The GCTefficacy and patient profile data may therefore be analyzed and takeninto consideration for future loans involving the specific GCTs.

In accordance with various aspects of the present disclosure, each loanmay be pooled together to create new securities that may be marketed andsold to investors. In approaching investors, the lender may use datasuch as types and coverage of warranties, market feedback, appetite forrisk to determine whether the new securities would be successful if thelender approaches a bank to securitize a loan.

Once GCT tracking is measured, adding additional GCT therapies to theloan pool will introduce new risk given that the efficacy and durabilityof the new GCT in the current beneficiary has yet to be determined, ormay have high error associated with efficacy given a small sample poolof patients that have undergone the new GCT. Various algorithms may beused to balance the portfolio, including analyzing fees paid to thelender based on the characteristics of the loan pool and the nature ofthe GCT therapies that comprise it.

In accordance with various aspects of the present disclosure, thealgorithms discussed herein may apply one or more heuristics to enable arapid decision process based on priorities and policies set by one ormore entities involved in the contemplated invention. This may beparticularly important in situations where the amount of time permittedto reach a decision is short. In certain embodiments, decision makingmay be done automatically by the AI within preset constraint limits.

In accordance with aspects of the present disclosure, the algorithm mayrequest assistance from one or more entities for guidance, when thealgorithm has incomplete information input and is unable to arrive to aconclusion.

Algorithms

Embodiments described herein may include the use of one or morealgorithms to enhance and/or optimize the features of variousembodiments. Algorithms may include, but are not limited to, forexample, artificial neural networks, multi-objective optimization,stochastic variables, probability and statistics, stochastic calculus,decision trees, random forests, linear and/or non-linear programming,regression, artificial intelligence, machine learning, Monte Carlo, orother techniques used for optimization and/or predictive analysis. It isunderstood by one skilled in the art that when these techniques arespecifically mentioned in the description of the algorithms below, thisdoes not exclude application of other techniques in the same algorithm.

Optimize Holdback Level and/or Timing

The holdback amount and timing may be determined by one or morealgorithms. These may be independently optimized or may besimultaneously optimized via multi-objective optimization. Inputs intothe algorithm may include one or more of the following pieces of dataregarding financial information from the company, such as pharmaceuticaltotal revenue, pharmaceutical revenue from target GCT sales,pharmaceutical revenue projections, projected therapeutic approvals over5 years that may impact revenue, pharmaceutical goal revenue recognitionper unit time (monthly, quarterly, yearly), and any other financialinformation from the company.

Optimize Interest Rate

The loan interest rate is the principal means for revenue generation. Itmay be independently optimized or may be simultaneously optimized viamulti-objective optimization. Given a set of GCTs and estimates for eachGCT efficacy, in conjunction with other market and/or cost data, aPareto frontier is generated identifying the optimal loan interest rate.

Forecast Future Revenue

Future portfolio revenue may be estimated by analyzing data includinghistoric and/or estimated GCT efficacy, GCT demand, GCT supply, and/orother input data. Stochastic analysis of outcomes under variousscenarios may be used to predict future revenues. Similar techniquessuch as stochastic calculus may be employed to predict the timeevolution of revenues under a variety of initial conditions.

Forecast Portfolio Balance

Stochastic analysis, stochastic calculus, and/or Monte Carlo techniquesmay be used to forecast the balance of various GCT used. Forecasting GCTbalance may be used to identify demand trends and may also be used toadjust loan interest rate and/or termination fee to optimally situatethe GCT portfolio with respect to market conditions.

Incorporation of New GCTs

Addition of a new GCT to an existing portfolio introduces risk as theefficacy of the new GCT may not be known with high precision. Thepotential variability of the GCT efficacy may lead to higher variance inforecasted revenues. Multi-objective optimization, artificial neuralnetworks, artificial intelligence, and/or Monte Carlo techniques may beemployed to quantify portfolio risk prior to adoption of a new GCT.

Adjust Interest Rate and/or Termination Fee for Individual GCTs

Portfolio optimization or prevailing market conditions may require theinterest rate to be different for different GCTs. GCTs will likely havedifferent efficacies, demands, supplies, and costs. This may lead tooptimization outcomes with different interest rates associated withdifferent GCTs. Multi-objective optimization, stochastic analysis,and/or Monte Carlo techniques may be employed to optimize theseparameters across a portfolio of GCTs.

Forecast Future Demand

Stochastic analysis and/or stochastic calculus may be used to forecastfuture demand for one or more GCTs. Historic demand, supply, estimatesof the treatable population, market expansion, and/or future costestimates may be leveraged by these techniques to estimate the futuredemand of GCTs under a variety of scenarios and initial conditions.

Forecast Future Supply

Stochastic analysis and/or stochastic calculus may be used to forecastfuture supply for one or more GCTs. Historic demand, supply, estimatesof the treatable population, market expansion, and/or future costestimates may be leveraged by these techniques to estimate the futuresupply of GCTs under a variety of scenarios and initial conditions.

Forecast Future Treatable Population

Stochastic analysis and/or stochastic calculus may be used to forecastfuture treatable population for one or more GCTs. Historic demand,estimates of the treatable population, market expansion, and/or futurecost estimates may be leveraged by these techniques to estimate thefuture treatable population of GCTs under a variety of scenarios andinitial conditions.

Forecast Future Costs

Stochastic analysis and/or stochastic calculus may be used to forecastfuture costs for one or more GCTs. Historic demand, estimates of thetreatable population, market expansion, and/or future cost estimates maybe leveraged by these techniques to estimate the future costs of GCTsunder a variety of scenarios and initial conditions.

Securitization Optimization

Determining which loans to bundle together for securitization may beaccomplished using multi-objective optimization, Pareto analysis, and/orstochastic analysis. Market conditions are examined to determine theoptimization factors and/or prioritization of such factors used in theanalysis. The result is a set of bundles suggested for securitization.These bundles may not be disjoint, allowing for selection preference byportfolio managers.

Algorithms, Generally

In accordance with various aspects of the present disclosure, thealgorithms discussed herein may, for example, apply more complexreasoning solutions in the area of multi-objective optimizationtechniques to make decisions regarding selection of borrower aggregatedrisk value, Loan Terms, and/or Loan Structure. Such multi-objectiveoptimization techniques may take in consideration different optimizationgoals of the entities involved. These techniques, and the success of thedecisions, may be based on information about the past decisions of thealgorithm in certain scenarios, and outcomes.

In accordance with various embodiments described herein, the algorithmsmay include one or more of the following methods of analysis andoptimization: case-based reasoning with displacement analysis,mechanical linkage analysis, optimized stiffness-displacement analysis,Procrustes-based pairwise optimization, blackboard framework, case-basedreasoning, CDR augmented two dimensional geometric overlay, directedgraph theory using tolerance analysis, displacement optimization,displacement optimization using genetic algorithms, displacementoptimization using penalty-function methods, finite element analysis,finite element and nonlinear rigid body dynamics analysis, forceanalysis using particle swarm optimization, force and moment analysis,force and moment equilibrium analysis, genetic-algorithm basedoptimization using screw theory, genetic algorithms, genetic algorithmoptimization, genetic algorithm optimization using finite elementanalysis, genetic algorithm-based optimized stiffness-displacementanalysis, geometric and kinetic model analysis, geometric constraintbased reasoning, geometric reasoning, geometry and graphical forceanalysis, geometry and rule-based approach, geometry-based reasoning,graph approach, graph theory using tolerance analysis, graph theoryusing tolerance factors, graph theory using tolerance normalization,group technology/neural network, heuristic preferences with screw-settheory, heuristic rule-base, heuristic rule-based approach withgeometric reasoning, kinematic algorithm, kinematic variation analysis,multi-criteria optimization, multi-objective optimization using aninterchange algorithm, neural network, non-optimized evolutionaryalgorithm, nonlinear optimization algorithm, object oriented reasoningwith fuzzy set optimization, parametric modeling, precedence matrix withgenetic algorithm, pseudo-gradient based optimization, qualitativerule-based analysis, rule induction and re-use, rule-based approach,rule-based approach augmented with various features, rule-based approachfeaturing graph analysis, stability analysis, tolerance sensitivityanalysis, rule-based with displacement analysis, stiffness-displacementanalysis, stress fracture analysis, swept volume analysis, toleranceanalysis, or any other suitable technology.

Constructive Example—Financing of Zolgensma® (OnasemnogeneAbeparvovec-Xioi) Administered to a HCT Beneficiary

The following is a hypothetical, illustrative scenario in which a payerutilizes the HCT financing instrument (referenced in this example as the“HCT instrument”) for a beneficiary requiring Zolgensma therapydelivered through the channel of a specialty pharmacy is offered.Zolgensma is one of two high-cost gene therapies currentlycommercialized in the United States and, as such, was chosen as apractical example to illustrate the application of the instrument andthe processes and procedures by which it can be utilized in conjunctionwith high-cost gene therapies that may be approved by the FDA. Inportions of this example it may be assumed, solely for the purposes ofthis illustration, that an association between the Applicant and themanufacturer of Zolgensma (AveXis/Novartis) exists, though no suchrelationship is currently in effect or likely to be in effect.AveXis/Novartis is not affiliated with the Applicant and has notendorsed, approved or otherwise opined on the HCT instrument either inpart or in whole. Use of Zolgensma in this illustrative example shouldnot be construed or interpreted to mean that the Applicant has made anyrepresentation concerning the utilization of the HCT instrument inconjunction with Zolgensma now or at any time in the future or that arelationship between the Applicant and the manufacturer(AveXis/Novartis) currently exists or may exist. Further, utilization ofthe HCT instrument by the payer, whether in part or whole, is notdependent on the pre-existence of any relationship between the Applicantand any pharmaceutical manufacturer.

Zolgensma, Onasemnogene abeparvovec, is a gene therapy developed byAveXis/Novartis and approved by the FDA in 2019 for use in childrenunder the age of two as a treatment option for spinal muscular atrophy,a neuromuscular disorder arising from mutations in the SMN1 gene thatresults in the loss of motor neurons, progressive muscle wasting and,frequently, death. Using the viral vector AAV9, Zolgensma works bydelivering to the recipient's affected motor neurons via intravenousinfusion a functional SMN1 transgene under the regulatory control ofsynthetic promoters. The therapy carries a list price of approximately$2.1MM.

Once a determination is made by a healthcare provider (HCP) thatZolgensma therapy would be of benefit to a covered beneficiary, aprocess begins whereby the payer is notified for purposes of grantingprior authorization. If the payer chooses to utilize the HCT instrument,the payer would contact the Applicant—acting as the financing company—toapply for a HCT instrument utilizing a set of formalized submissionprocedures and guidelines established by the Applicant. Upon receipt ofthe payer's HCT instrument application, the Applicant would determinethe terms of financing arrangement based on the criteria previouslyoutlined in this claim and in conjunction with any holdback percentagethat AveXis/Novartis may utilize as a form of subvention to financingalong with the availability of a value based agreement.

In this hypothetical example, a warranty may be available to the payerfor a premium in which the efficacy of Zolgensma may be guaranteed inproportion to the remaining loan payments. The period of warrantyeffectiveness along with the tenor of the loan financing would establishthe episode of care. In other embodiments, the episode of care begins atthe execution of the term sheet or loan documents, or at another pointin time decided upon by the lender and key stakeholders (e.g., thepayer, manufacturer, etc.). With respect to Zolgensma, efficacy may bedefined as preventing death or the need for permanent ventilatorysupport consisting of >16 hours of respiratory assistance per daycontinuously for >14 days or some other metric consistent with outcomecriteria established during the Zolgensma clinical or post-marketingevaluation periods. Other metrics such as scoring on the Children'sHospital of Philadelphia Infant Test of Neuromuscular Disorders(CHOP-INTEND) may be utilized at the discretion of the underwritingparty at their sole discretion. The warranty may be provided byAveXis/Novartis, an AveXis/Novartis affiliate, the Applicant, anaffiliate of the Applicant or a separate third-party underwriter.

For this hypothetical, it is assumed that the loan principal consists ofthe $2.1MM cost of Zolgensma and a $200,000 premium for the warranty,and $50,000 infusion costs ($2.305MM total), to be repaid over afour-year episode of care with 8% fixed interest, compounded monthlyover the instrument's tenor ($2,753,777.64 total principal and interestpayments, paid in $57,370.37 monthly installments) with a 10% holdback.

If the payer agrees to these terms, the payer would grant authorizationfor Zolgensma to the HCP who would then receive the therapy via“white-bag” from AveXis/Novartis, or an associated specialty pharmacy(e.g. Orsini, Accredo) dispensing Zolgensma, upon “closing” of the loan.At closing, the dispensing entity would receive from the Applicant(acting as the source of financing) 77% ($1.617MM) of the $2.1MMZolgensma cost. The HCP would then administer the therapy to thebeneficiary. After a two-week determination period in which thebeneficiary was monitored by an independent, third-party outcomes basedadminister (OBA), the dispensing entity would receive an additional 13%($273,000) if certain criteria were met (e.g. whether the beneficiarywas still alive and not requiring extensive ventilator support). At thistime, the loan would be finalized and the payer would begin makingperiodic principal (inclusive of the cost of Zolgensma plus the warrantyproduct premium, initial outcomes benefit administrator (OBA) fees, andprocedure-related costs) and interest payments to the Applicant. If thedetermination criteria were not met (e.g. the beneficiary did notsurvive) the loan would unwind and the warranty would pay the remainingloan liability and prepayment penalty.

Over the course of the next four years, i.e., in this example, thecontractually defined “episode of care”, the payer would make continuedmonthly principal and interest payments of $57,370.37 to the Applicantand the beneficiary would be monitored by the OBA to assess whether theconditions of the warranty have been satisfied. If, after four years,the provisions of the warranty were not triggered and the payersatisfied their loan obligation, AveXis/Novartis, or the associateddispensing specialty pharmacy, would receive a bullet payment in theamount of $210,000 or 10% of the cost of Zolgensma, and the episode ofcare would conclude.

Furthermore, the aforementioned loan may be part of a bundle of loansfor purposes of securitization. For example, once an HCT financing loanportfolio has been created (with “sufficiency” defined, for example, interms of the risk profile and diversity of the borrowers, the diversityof GCTs covered, the diversity of GCT manufacturers, in addition toother metrics), the lender (or its designated party, or another party)can bundle these loans for the purposes of securitization anddistribution to the broader financial markets. For example, thesecuritization basket may comprise 200-300 HCT financing loans with anotional value of 300MM-500MM USD. Credit rating, average coupon,position sizing, and the like, can be determined at the time ofcreation. Tranching of the loan cash flows can be determined during thecreation of the securitization and subject to various market conditionsthat would affect the attractiveness of the securities to the market.Loans associated with multiple GCTs, various payer types, differing loantenors, and the like, may be ideal to achieve the maximumdiversification benefit from the total portfolio and to reduce the riskprofile of both the overall loan basket as well as the individualtranches.

Software, Computer System, and Network Environment

Certain embodiments described herein make use of computer algorithms inthe form of software instructions executed by a computer processor. Incertain embodiments, the software instructions include a machinelearning module, also referred to herein as artificial intelligencesoftware. As used herein, a machine learning module refers to a computerimplemented process (e.g., a software function) that implements one ormore specific machine learning algorithms, such as an artificial neuralnetwork (ANN), random forest, decision trees, support vector machines,and the like, in order to determine, for a given input, one or moreoutput values. In certain embodiments, the input comprises alphanumericdata which can include numbers, words, phrases, or lengthier strings,for example. In certain embodiments, the one or more output valuescomprise values representing numeric values, words, phrases, or otheralphanumeric strings. In certain embodiments, the one or more outputvalues comprise an identification of one or more response strings (e.g.,selected from a database).

For example, a machine learning module may receive as input a textualstring (e.g., entered by a human user, for example) and generate variousoutputs. For example, the machine learning module may automaticallyanalyze the input alphanumeric string(s) to determine output valuesclassifying a content of the text (e.g., an intent), e.g., as in naturallanguage understanding (NLU). In certain embodiments, a textual stringis analyzed to generate and/or retrieve an output alphanumeric string.For example, a machine learning module may be (or include) naturallanguage processing (NLP) software. Examples of NLP software include,without limitation, BERT (Bidirectional Encoder Representations fromTransformers), Question Answer software (e.g., IR-based factoid QuestionAnswering, knowledge-based Question Answering, and multiple sourceQuestion Answering (e.g., IBM's Watson). In certain embodiments, machinelearning modules for NLP are trained using datasets such as StanfordQuestion Answering Dataset (SQuAD), WikiQA dataset, TREC-QA dataset,NewsQA dataset.

In certain embodiments, machine learning modules implementing machinelearning techniques are trained, for example using datasets that includecategories of data described herein. Such training may be used todetermine various parameters of machine learning algorithms implementedby a machine learning module, such as weights associated with layers inneural networks. In certain embodiments, once a machine learning moduleis trained, e.g., to accomplish a specific task such as identifyingcertain response strings, values of determined parameters are fixed andthe (e.g., unchanging, static) machine learning module is used toprocess new data (e.g., different from the training data) and accomplishits trained task without further updates to its parameters (e.g., themachine learning module does not receive feedback and/or updates). Incertain embodiments, machine learning modules may receive feedback,e.g., based on user review of accuracy, and such feedback may be used asadditional training data, to dynamically update the machine learningmodule. In certain embodiments, two or more machine learning modules maybe combined and implemented as a single module and/or a single softwareapplication. In certain embodiments, two or more machine learningmodules may also be implemented separately, e.g., as separate softwareapplications. A machine learning module may be software and/or hardware.For example, a machine learning module may be implemented entirely assoftware, or certain functions of a ANN module may be carried out viaspecialized hardware (e.g., via an application specific integratedcircuit (ASIC)).

As shown in FIG. 4, an implementation of a network environment 400 foruse in providing systems, methods, and architectures as described hereinis shown and described. In brief overview, referring now to FIG. 4, ablock diagram of an exemplary cloud computing environment 400 is shownand described. The cloud computing environment 400 may include one ormore resource providers 402 a, 402 b, 402 c (collectively, 402). Eachresource provider 402 may include computing resources. In someimplementations, computing resources may include any hardware and/orsoftware used to process data. For example, computing resources mayinclude hardware and/or software capable of executing algorithms,computer programs, and/or computer applications. In someimplementations, exemplary computing resources may include applicationservers and/or databases with storage and retrieval capabilities. Eachresource provider 402 may be connected to any other resource provider402 in the cloud computing environment 400. In some implementations, theresource providers 402 may be connected over a computer network 408.Each resource provider 402 may be connected to one or more computingdevice 404 a, 404 b, 404 c (collectively, 404), over the computernetwork 408.

The cloud computing environment 400 may include a resource manager 406.The resource manager 406 may be connected to the resource providers 402and the computing devices 404 over the computer network 408. In someimplementations, the resource manager 406 may facilitate the provisionof computing resources by one or more resource providers 402 to one ormore computing devices 404. The resource manager 406 may receive arequest for a computing resource from a particular computing device 404.The resource manager 406 may identify one or more resource providers 402capable of providing the computing resource requested by the computingdevice 404. The resource manager 406 may select a resource provider 402to provide the computing resource. The resource manager 406 mayfacilitate a connection between the resource provider 402 and aparticular computing device 404. In some implementations, the resourcemanager 406 may establish a connection between a particular resourceprovider 402 and a particular computing device 404. In someimplementations, the resource manager 406 may redirect a particularcomputing device 404 to a particular resource provider 402 with therequested computing resource.

FIG. 5 shows an example of a computing device 500 and a mobile computingdevice 550 that can be used to implement the techniques described inthis disclosure. The computing device 500 is intended to representvarious forms of digital computers, such as laptops, desktops,workstations, personal digital assistants, servers, blade servers,mainframes, and other appropriate computers. The mobile computing device550 is intended to represent various forms of mobile devices, such aspersonal digital assistants, cellular telephones, smart-phones, andother similar computing devices. The components shown here, theirconnections and relationships, and their functions, are meant to beexamples only, and are not meant to be limiting.

The computing device 500 includes a processor 502, a memory 504, astorage device 506, a high-speed interface 508 connecting to the memory504 and multiple high-speed expansion ports 510, and a low-speedinterface 512 connecting to a low-speed expansion port 514 and thestorage device 506. Each of the processor 502, the memory 504, thestorage device 506, the high-speed interface 508, the high-speedexpansion ports 510, and the low-speed interface 512, are interconnectedusing various busses, and may be mounted on a common motherboard or inother manners as appropriate. The processor 502 can process instructionsfor execution within the computing device 500, including instructionsstored in the memory 504 or on the storage device 506 to displaygraphical information for a GUI on an external input/output device, suchas a display 516 coupled to the high-speed interface 508. In otherimplementations, multiple processors and/or multiple buses may be used,as appropriate, along with multiple memories and types of memory. Also,multiple computing devices may be connected, with each device providingportions of the necessary operations (e.g., as a server bank, a group ofblade servers, or a multi-processor system). Thus, as the term is usedherein, where a plurality of functions are described as being performedby “a processor”, this encompasses embodiments wherein the plurality offunctions are performed by any number of processors (one or more) of anynumber of computing devices (one or more). Furthermore, where a functionis described as being performed by “a processor”, this encompassesembodiments wherein the function is performed by any number ofprocessors (one or more) of any number of computing devices (one ormore) (e.g., in a distributed computing system).

The memory 504 stores information within the computing device 500. Insome implementations, the memory 504 is a volatile memory unit or units.In some implementations, the memory 504 is a non-volatile memory unit orunits. The memory 504 may also be another form of computer-readablemedium, such as a magnetic or optical disk.

The storage device 506 is capable of providing mass storage for thecomputing device 500. In some implementations, the storage device 506may be or contain a computer-readable medium, such as a floppy diskdevice, a hard disk device, an optical disk device, or a tape device, aflash memory or other similar solid state memory device, or an array ofdevices, including devices in a storage area network or otherconfigurations. Instructions can be stored in an information carrier.The instructions, when executed by one or more processing devices (forexample, processor 502), perform one or more methods, such as thosedescribed above. The instructions can also be stored by one or morestorage devices such as computer- or machine-readable mediums (forexample, the memory 504, the storage device 506, or memory on theprocessor 502).

The high-speed interface 508 manages bandwidth-intensive operations forthe computing device 500, while the low-speed interface 512 manageslower bandwidth-intensive operations. Such allocation of functions is anexample only. In some implementations, the high-speed interface 508 iscoupled to the memory 504, the display 516 (e.g., through a graphicsprocessor or accelerator), and to the high-speed expansion ports 510,which may accept various expansion cards (not shown). In theimplementation, the low-speed interface 512 is coupled to the storagedevice 506 and the low-speed expansion port 514. The low-speed expansionport 514, which may include various communication ports (e.g., USB,Bluetooth®, Ethernet, wireless Ethernet) may be coupled to one or moreinput/output devices, such as a keyboard, a pointing device, a scanner,or a networking device such as a switch or router, e.g., through anetwork adapter.

The computing device 500 may be implemented in a number of differentforms, as shown in the figure. For example, it may be implemented as astandard server 520, or multiple times in a group of such servers. Inaddition, it may be implemented in a personal computer such as a laptopcomputer 522. It may also be implemented as part of a rack server system524. Alternatively, components from the computing device 500 may becombined with other components in a mobile device (not shown), such as amobile computing device 550. Each of such devices may contain one ormore of the computing device 500 and the mobile computing device 550,and an entire system may be made up of multiple computing devicescommunicating with each other.

The mobile computing device 550 includes a processor 552, a memory 564,an input/output device such as a display 554, a communication interface566, and a transceiver 568, among other components. The mobile computingdevice 550 may also be provided with a storage device, such as amicro-drive or other device, to provide additional storage. Each of theprocessor 552, the memory 564, the display 554, the communicationinterface 566, and the transceiver 568, are interconnected using variousbuses, and several of the components may be mounted on a commonmotherboard or in other manners as appropriate.

The processor 552 can execute instructions within the mobile computingdevice 550, including instructions stored in the memory 564. Theprocessor 552 may be implemented as a chipset of chips that includeseparate and multiple analog and digital processors. The processor 552may provide, for example, for coordination of the other components ofthe mobile computing device 550, such as control of user interfaces,applications run by the mobile computing device 550, and wirelesscommunication by the mobile computing device 550.

The processor 552 may communicate with a user through a controlinterface 558 and a display interface 556 coupled to the display 554.The display 554 may be, for example, a TFT (Thin-Film-Transistor LiquidCrystal Display) display or an OLED (Organic Light Emitting Diode)display, or other appropriate display technology. The display interface556 may comprise appropriate circuitry for driving the display 554 topresent graphical and other information to a user. The control interface558 may receive commands from a user and convert them for submission tothe processor 552. In addition, an external interface 562 may providecommunication with the processor 552, so as to enable near areacommunication of the mobile computing device 550 with other devices. Theexternal interface 562 may provide, for example, for wired communicationin some implementations, or for wireless communication in otherimplementations, and multiple interfaces may also be used.

The memory 564 stores information within the mobile computing device550. The memory 564 can be implemented as one or more of acomputer-readable medium or media, a volatile memory unit or units, or anon-volatile memory unit or units. An expansion memory 574 may also beprovided and connected to the mobile computing device 550 through anexpansion interface 572, which may include, for example, a SIMM (SingleIn Line Memory Module) card interface. The expansion memory 574 mayprovide extra storage space for the mobile computing device 550, or mayalso store applications or other information for the mobile computingdevice 550. Specifically, the expansion memory 574 may includeinstructions to carry out or supplement the processes described above,and may include secure information also. Thus, for example, theexpansion memory 574 may be provide as a security module for the mobilecomputing device 550, and may be programmed with instructions thatpermit secure use of the mobile computing device 550. In addition,secure applications may be provided via the SIMM cards, along withadditional information, such as placing identifying information on theSIMM card in a non-hackable manner.

The memory may include, for example, flash memory and/or NVRAM memory(non-volatile random access memory), as discussed below. In someimplementations, instructions are stored in an information carrier. Theinstructions, when executed by one or more processing devices (forexample, processor 552), perform one or more methods, such as thosedescribed above. The instructions can also be stored by one or morestorage devices, such as one or more computer- or machine-readablemediums (for example, the memory 564, the expansion memory 574, ormemory on the processor 552). In some implementations, the instructionscan be received in a propagated signal, for example, over thetransceiver 568 or the external interface 562.

The mobile computing device 550 may communicate wirelessly through thecommunication interface 566, which may include digital signal processingcircuitry where necessary. The communication interface 566 may providefor communications under various modes or protocols, such as GSM voicecalls (Global System for Mobile communications), SMS (Short MessageService), EMS (Enhanced Messaging Service), or MMS messaging (MultimediaMessaging Service), CDMA (code division multiple access), TDMA (timedivision multiple access), PDC (Personal Digital Cellular), WCDMA(Wideband Code Division Multiple Access), CDMA2000, or GPRS (GeneralPacket Radio Service), among others. Such communication may occur, forexample, through the transceiver 568 using a radio-frequency. Inaddition, short-range communication may occur, such as using aBluetooth®, Wi-Fi™, or other such transceiver (not shown). In addition,a GPS (Global Positioning System) receiver module 570 may provideadditional navigation- and location-related wireless data to the mobilecomputing device 550, which may be used as appropriate by applicationsrunning on the mobile computing device 550.

The mobile computing device 550 may also communicate audibly using anaudio codec 560, which may receive spoken information from a user andconvert it to usable digital information. The audio codec 560 maylikewise generate audible sound for a user, such as through a speaker,e.g., in a handset of the mobile computing device 550. Such sound mayinclude sound from voice telephone calls, may include recorded sound(e.g., voice messages, music files, etc.) and may also include soundgenerated by applications operating on the mobile computing device 550.

The mobile computing device 550 may be implemented in a number ofdifferent forms, as shown in the figure. For example, it may beimplemented as a cellular telephone 580. It may also be implemented aspart of a smart-phone 582, personal digital assistant, or other similarmobile device.

Various implementations of the systems and techniques described here canbe realized in digital electronic circuitry, integrated circuitry,specially designed ASICs (application specific integrated circuits),computer hardware, firmware, software, and/or combinations thereof.These various implementations can include implementation in one or morecomputer programs that are executable and/or interpretable on aprogrammable system including at least one programmable processor, whichmay be special or general purpose, coupled to receive data andinstructions from, and to transmit data and instructions to, a storagesystem, at least one input device, and at least one output device.

These computer programs (also known as programs, software, softwareapplications or code) include machine instructions for a programmableprocessor, and can be implemented in a high-level procedural and/orobject-oriented programming language, and/or in assembly/machinelanguage. As used herein, the terms machine-readable medium andcomputer-readable medium refer to any computer program product,apparatus and/or device (e.g., magnetic discs, optical disks, memory,Programmable Logic Devices (PLDs)) used to provide machine instructionsand/or data to a programmable processor, including a machine-readablemedium that receives machine instructions as a machine-readable signal.The term machine-readable signal refers to any signal used to providemachine instructions and/or data to a programmable processor.

To provide for interaction with a user, the systems and techniquesdescribed here can be implemented on a computer having a display device(e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor)for displaying information to the user and a keyboard and a pointingdevice (e.g., a mouse or a trackball) by which the user can provideinput to the computer. Other kinds of devices can be used to provide forinteraction with a user as well; for example, feedback provided to theuser can be any form of sensory feedback (e.g., visual feedback,auditory feedback, or tactile feedback); and input from the user can bereceived in any form, including acoustic, speech, or tactile input.

The systems and techniques described here can be implemented in acomputing system that includes a back end component (e.g., as a dataserver), or that includes a middleware component (e.g., an applicationserver), or that includes a front end component (e.g., a client computerhaving a graphical user interface or a Web browser through which a usercan interact with an implementation of the systems and techniquesdescribed here), or any combination of such back end, middleware, orfront end components. The components of the system can be interconnectedby any form or medium of digital data communication (e.g., acommunication network). Examples of communication networks include alocal area network (LAN), a wide area network (WAN), and the Internet.

The computing system can include clients and servers. A client andserver are generally remote from each other and typically interactthrough a communication network. The relationship of client and serverarises by virtue of computer programs running on the respectivecomputers and having a client-server relationship to each other.

In some implementations, certain modules described herein can beseparated, combined or incorporated into single or combined modules. Anymodules depicted in the figures are not intended to limit the systemsdescribed herein to the software architectures shown therein.

FIG. 6 illustrates a packaged pharmaceutical composition or kit 600,according to various aspects of the present embodiments. The kit 600 mayinclude packaging 610 which may include a label 620 that displays a barcode 625 and/or a National Drug Code (NDC) 630. The kit 600 may alsoinclude a vessel 640 for containing the drug/pharmaceutical composition.The vessel 640 may also include a label 620 that displays a bar code 625and/or a National Drug Code (NDC) 630. The kit 600 may also include aninsert 650 with information about the drug/pharmaceutical composition.Alternatively, or in addition, the insert 650 may include a descriptionindicating how the drug is financed. For example, in certainembodiments, the insert 650 includes a description indicating the drugis financed according to any of the HCT financing embodiments describedherein. In some embodiments, the insert 650 may include one or morefolded pieces of paper with information written thereon (for example,one side or on both sides). In some embodiments, the insert 650 may bedisposed within the packaging 610. In some embodiments, the insert 650may be wrapped around the vessel 640 (for example, in embodiments inwhich the vessel 640 is substantially cylindrical). In some embodiments,the insert 650 may be attached to the side of the vessel 640 (forexample, in embodiment in which the vessel 640 has a substantiallysquare or rectangular cross section). In some embodiments, the insertmay be disposed between the label 620 and the vessel 640 and/orpackaging 610 (i.e., “behind” the label 620). The vessel 640 may be orinclude a pharmaceutically acceptable vessel. The vessel 640 may besealed or secured in accordance with industry-accepted practices andprotocols. In certain embodiments, the insert 650 is displayed via awebsite or other computer accessible network.

Constructive Example—the Following is an Example Term Sheet for anInstrument (e.g., Loan) that is Part of a High Cost Therapy (HCT)Financing, According to Certain Embodiments Described Herein [Formof]Summary of Indicative Terms and Conditions CTxO Loan

[The terms and conditions summarized in this term sheet are provided fordiscussion purposes only and do not constitute an offer, agreement, orcommitment. The terms and conditions contained herein are subject to thesatisfactory review and execution of documentation. The parties agreeand acknowledge that this Summary of Indicative Terms and Conditionsconstitutes a non-binding letter of intention and obligates neitherparty to proceed with or consummate the transaction described herein.Except as provided in the next sentence, this Summary of IndicativeTerms and Conditions does not and is not intended to create any legalobligation or enforceable right in any party.

The parties hereto acknowledge that “CTxO” and the related term, “CRxO,”are trademarked. Furthermore, the loan structure contained herein, aswell as anything derived from its concepts, are claimed as trade secretsof Octaviant Financial, Inc., subject to non-disclosure agreements, arepatent protected and copyrighted.]

Elements of different implementations described herein may be combinedto form other implementations not specifically set forth above. Elementsmay be left out of the processes, computer programs, databases, etc.described herein without adversely affecting their operation. Inaddition, the logic flows depicted in the figures do not require theparticular order shown, or sequential order, to achieve desirableresults. Various separate elements may be combined into one or moreindividual elements to perform the functions described herein.

Throughout the description, where apparatus and systems are described ashaving, including, or comprising specific components, or where processesand methods are described as having, including, or comprising specificsteps, it is contemplated that, additionally, there are apparatus, andsystems of the present invention that consist essentially of, or consistof, the recited components, and that there are processes and methodsaccording to the present invention that consist essentially of, orconsist of, the recited processing steps.

It should be understood that the order of steps or order for performingcertain action is immaterial so long as the invention remains operable.Moreover, two or more steps or actions may be conducted simultaneously.

While the invention has been particularly shown and described withreference to specific preferred embodiments, it should be understood bythose skilled in the art that various changes in form and detail may bemade therein without departing from the spirit and scope of theinvention as defined by the appended claims.

1. A method for assessment of an application for an instrument, and uponapproval, for determination of one or more terms of the instrument, forfinancing one or more of (i), (ii), and (iii) as follows (collectively,the HCT financing): (i) a high cost therapy (HCT) to be administered toa HCT beneficiary, (ii) bundled expenses for pre- and/or post-therapytherapeutic treatments and/or services rendered to the HCT beneficiaryrelated to an underlying medical condition of the HCT beneficiaryaddressed by the HCT, and/or monitoring and/or analysis of the efficacyof the HCT administered to the HCT beneficiary, and (iii) an associatedperformance-based guaranty of the efficacy of the HCT administered tothe HCT beneficiary, wherein said instrument is structured in a mannerto facilitate portability of said instrument over the tenor of theinstrument, the method comprising: (a) receiving, by a processor of acomputing device, a first set of data of the application for theinstrument from a remote client computer; and (b) determining, by theprocessor, according to one or more factors, an approval of and/or astructure of the instrument using the first set of data, saiddetermining performed such that: (i) said HCT financing comprisesbundled expenses for pre- and/or post-therapy therapeutic treatmentsand/or services rendered to the HCT beneficiary related to an underlyingmedical condition of the HCT beneficiary addressed by the HCT, and/ormonitoring and/or analysis of the efficacy of the HCT administered tothe HCT beneficiary, said bundled expenses being compensated for acontractually-defined episode of care, wherein said episode of care is atime period associated with the HCT for which a bundled payment is made;and (ii) said HCT financing comprises a multi-year repayment periodhaving a tenor that ends contiguously with a defined episode of care,wherein said episode of care is contractually defined to establish apre-existing condition of the HCT beneficiary, thereby facilitatingportability and/or transferability of associated liability from oneparty to another party while the HCT beneficiary is considered to havethe pre-existing condition; (c) dynamically updating, by the processor,at least one of the one or more factors accounted for in step (b), suchthat the determination in step (b) accounts for one or more changingfactors and permits the determination in step (b) to be made where timepermitted to reach a decision is short; and (d) transmitting, by theprocessor, the determination in step (b) to the remote client computer.2. The method of claim 1, further comprising: (e) identifying a bundleof cash flow receivables arising from HCT financings to include in asecuritization basket and determining one or more terms of thesecuritization basket.
 3. The method of claim 1, wherein the high-costinitial treatment is a drug having a National Drug Code (NDC) thatidentifies mechanism of payment via the HCT financing.
 4. The method ofclaim 1, wherein step (b) comprises determining, by the processor, thestructure of the instrument, wherein the instrument comprises amulti-year payment plan having a tenor that matches said episode ofcare, and wherein the payment plan comprises: an upfront draw to be paidupon administration of a high-cost initial treatment to the HCTbeneficiary, and a second, subsequent payment to be made upon a finalclose of the payment plan following and contingent upon a determinationof initial efficacy of the HCT for the HCT beneficiary.
 5. The method ofclaim 4, wherein the final close is in an amount that covers theremainder of the cost of the HCT, which may or may not include theassociated services, less a holdback to be paid by the manufacturer ofthe high cost initial treatment.
 6. The method of claim 5, wherein thepayment plan comprises a senior tranche amortization period, and whereinthe holdback is subordinate to the senior tranche.
 7. The method ofclaim 4, wherein the upfront draw is paid off upon a determination ofinitial non-efficacy of the initial treatment in the HCT beneficiary. 8.The method of claim 1, wherein step (b) comprises determining, by theprocessor, a structure of the instrument of the HCT financing based onone or more of the following: total cost of the HCT; credit rating of aborrower; current debt service of the borrower; assessment of ability ofthe borrower to collateralize the instrument; assessment of financialsolvency and cash flow generating capability of the borrower; assessmentof desire of the manufacturer to provide subvention; amount, if any, ofmanufacturer holdback; projected efficacy of the HCT; nature, cost andterms of an associated warranty; duration of the warranty; theexistence, if any, and cost of a current, non-HCT or HCT standard ofcare therapy; level of an interest rate benchmark for a variable rateloan; prevailing market interest rates for loans of similar tenor andrisk profile; market-wide default rates; existence, if any, ofprepayment penalties; and size of any upfront draws.
 9. A system forassessment of an application for an instrument, and upon approval, fordetermination of one or more terms of the instrument that forms part ofa high cost therapy (HCT) financing, the system comprising: a processorof a computing device; and a memory having instructions stored thereon,wherein the instructions, when executed by the processor, cause theprocessor to: (a) receive a first set of data of the application for theinstrument from a remote client computer; (b) determine, according toone or more factors, an approval of and/or a structure of theinstrument, said determining performed such that: Ii) said HCT financingcomprises bundled expenses for pre- and/or post-therapy therapeutictreatments and/or services rendered to the HCT beneficiary related to anunderlying medical condition of the HCT beneficiary addressed by theHCT, and/or monitoring and/or analysis of the efficacy of the HCTadministered to the HCT beneficiary, said bundled expenses beingcompensated for a contractually-defined episode of care, wherein saidepisode of care is a time period associated with the HCT for which abundled payment is made; and (ii) said HCT financing comprises amulti-year payment plan having a tenor that ends contiguously with adefined episode of care, wherein said episode of care is contractuallydefined to establish a pre-existing condition of the HCT beneficiary,thereby facilitating portability and/or transferability of associatedliability from one party to another party while the HCT beneficiary isconsidered to have the pre-existing condition, (c) dynamically update atleast one of the one or more factors accounted for in step (b), suchthat the determination in step (b) accounts for one or more changingfactors and permits the determination in step (b) to be made where timepermitted to reach a decision is short; and (d) transmit thedetermination in step (b) to the remote client computer.
 10. The methodof claim 1, wherein said HCT financing is a payment plan.
 11. The methodof claim 1, wherein said HCT financing is a loan.
 12. The method ofclaim 1, wherein said HCT financing comprises an upfront draw paid to aparty that provides and/or administers the HCT to the HCT beneficiaryand is made at or near the time of administration of the HCT to the HCTbeneficiary, and wherein said HCT financing comprises a second draw paidwithin an agreed-upon period of time after administration of the HCT andupon determination of initial efficacy of the HCT for the HCTbeneficiary.
 13. The method of claim 19, wherein said upfront draw is aninitial use of proceeds and said second draw is a subsequent use ofproceeds.
 14. The method of claim 1, further comprising: (e) identifyinga bundle of loans to include in a securitization basket and determiningone or more terms of the securitization basket.
 15. The method of claim1, wherein step (b) comprises determining a structure of the instrumentof the HCT financing based on one or more of the following: total costof the HCT; credit rating of a creditee; current debt service of thecreditee; assessment of ability of the creditee to collateralize theinstrument; assessment of financial solvency and cash flow generatingcapability of the creditee; assessment of desire of the manufacturer toprovide subvention; amount, if any, of manufacturer holdback; projectedefficacy of the HCT; nature, cost and terms of an associated warranty;duration of the warranty; the existence, if any, and cost of a current,non-HCT or HCT standard of care therapy; level of an interest ratebenchmark for a variable rate loan; prevailing market interest rates forloans of similar tenor and risk profile; market-wide default rates;existence, if any, of prepayment penalties; and size of any upfrontdraws.
 16. The method of claim 1, wherein said HCT financing comprisesan upfront draw paid to a party that provides and/or administers the HCTto the HCT beneficiary and is made at or near the time of administrationof the HCT to the HCT beneficiary.
 17. The method of claim 1, whereinsaid HCT financing comprises a premium payment for a value basedagreement (VBA) structured as a performance guaranty of initial efficacyof the HCT for the HCT beneficiary.
 18. The method of claim 1, whereinsaid HCT financing comprises a second draw paid within an agreed-uponperiod of time after administration of the HCT and upon determination ofinitial efficacy of the HCT for the HCT beneficiary. 19-20. (canceled)21. The method of claim 1, wherein said HCT financing comprises a valuebased agreement having a period that ends contiguously with a definedepisode of care, wherein said episode of care is contractually definedto establish a pre-existing condition of the HCT beneficiary, therebyfacilitating portability and/or transferability of associated liabilitywhile the HCT beneficiary is considered to have the pre-existingcondition.
 22. The method of claim 1, wherein the one or more factorsdynamically updated in step (c) comprises one or more of the following:(i) data regarding a total cost of care, which includes one or more ofthe following: costs charged by a formulating pharmacy, cost charged bya therapeutic manufacturer, and a value-based agreement premium; (ii) adetermination period for determination of initial efficacy of the HCTfor the HCT beneficiary, (iii) data regarding timing of cost of careover the determination period, (iv) an amount and/or percent of anupfront draw, (v) data regarding a borrower and/or its credit data, (vi)data regarding the manufacturer preferred loan terms, which includes oneor more of the following: amount and/or timing of cash payments, andsize and/or timing of holdback terms; (vii) the stated and/orprobabilistically calculated efficacy of the HCT; (viii) data on anassociated warranty, which includes one or more of the following: itsnature, its cost, and its terms; (ix) prevailing variable interest ratefloors established by a benchmark; (x) current market interest rates forloans of similar tenor and risk profile; (xi) market-wide default rates;(xii) pre-determined penalties for pre-payment; and (xiii) aggregateand/or individual risks.
 23. The method of claim 1, comprisingauto-filling an offer term sheet and/or loan agreement document by theprocessor.